LSF Magazine Winter 2015

LSF MAGAZINEWinter 2015 Telling the Story of Biotechnology

special issue:

Global Biotech

2 LSF Magazine Winter 2015

Departments04 LSF News

06 LSF Events

12 Educators’ CornerBio-Rad’s Gift

14 Biotech BookshelfBiotechnology in Africa and Swiss Made

16 LSF Oral History ProgramDennis Gillings, “Calculated Risk and Reward” George Poste, “Embracing Complexity”

20 Gems from the ArchiveThe first Hambrecht & Quist Healthcare Conference, January 1983

22 ObituaryRobert Schimke (1932-2014)

24 In ConversationFlorence Wambugu, Kenyan scientist and technology advocate

52 Photo FinishThe Art of Robert Schimke

Features28 Global Biotech Centers

Singapore, Cambridge, Dubai, Shenzhen, and Santiago

38 Vital ToolsA Brief History of CHO Cells

48 Global Biotech PhilanthropyDiagnostics for All Erbitux and the Manzanar Project

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28

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Winter 2015 LSF Magazine 3

Executive Editor Mark Jones

Editor Marie Daghlian

Production Manager Gavin Rynne

Design/Layout Carol Collier Zachary Rais-Norman

Contributors Brian Dick Michael Hammerschmidt Victor McElheny Eddie Patterson Gavin Rynne Ramya Rajagopalan Barri Segal Ian Signer Hallam Stevens Kevin Vickery

© Copyright 2015 Life Sciences Foundation All rights reserved

From the editorThis issue of LSF Magazine contains stories

on global developments in biotechnology. Here’s a brief history lesson:

At the end of the nineteenth century, Germany led the world in science and indus-try. Over the next three decades, the world’s technoscientific center of gravity migrated west, to North America. Public and private institu-tions in the United States expanded support for scientific research and the nation’s technologi-cal capabilities grew.

In the 1920s, the American economy began exercising innovative capabilities across a wide range of industries. Even through the Great De-pression, with much of the country’s labor force idled, US corporations built industrial laborato-ries and testing facilities, made inventions, and stoked the nation’s economic furnace.

In the 1940s, the war effort ignited further rounds of innovation. Scientists and engineers employed by universities, federal agencies, and private contractors were pressed into research duty. In the postwar period, scientific and tech-nological progress became a national security matter of the highest priority.

In the 1950s and 1960s, venture capital, skimmed from the wealth of the most produc-tive economy in human history, generated a wild blossoming of high technologies. Science and capital combined to transform California’s Santa Clara Valley and Boston suburbs along Route 128 into vibrant technopoles.

When molecular biology came to practical fruition in the 1970s with the invention of recombinant DNA and hybridoma technol-ogies, conditions conducive to life science enterprise were already set in place in America. The emergence of the biotechnology industry can be attributed to powerful economic forces unleashed in the United States in previous decades.

At the end of the twentieth century, America led the world in bioscience and industry. In 2015, it still does, but the future is uncertain. The world economy has become globalized. It is characterized by new developmental logics.

International trade has intensified and accelerated. Information technologies permit knowledge and capital to circulate and settle

virtually anywhere on the planet. Time and space have been compressed, and many prob-lems once posed by distances and borders have been dissolved. National, regional, and local economies that used to operate provincially have been connected, integrated, and made interdependent.

The biotech industry has been enmeshed in this process for at least two decades. The spectacular rise of the industry’s contract research and manufacturing sectors, and the formation of foreign subsidiaries by biotech operations large and small, reflect opportunities and needs to access emerging markets. At the same time, cities and states all over the global map have reconfigured policies to attract biotech enterprises and spur the creation of new regional industries.

So far, self-sustaining centers of biotech innovation have been established only in places endowed with strong science, entrepreneurial cultures, business-friendly policies, sturdy support infrastructures, and skilled workers. Many developed countries in Europe and Asia possess these attributes and are racing to catch up with the United States.

Other nations are making substantial invest-ments in education and research in hopes of getting into the game (Brazil, India, and South Korea are prime examples). They are develop-ing manufacturing capabilities and positioning themselves, through a host of inducements, as outsourcing destinations and gateways to emerging markets.

In the near term, poor countries in Africa, Asia, Latin America, and the Middle East have virtually no chance to participate in the global biotech economy as producers, but with further economic development, they may generate enough wealth to become purchasers. Until then, they will remain largely dependent on charity.

History matters in this evolutionary process. Head starts and deficits matter, but the future hasn’t been written. The twentieth century was the “American century.” The twenty-first is a question mark.

Mark Jones

A message from Board Chair Carl Feldbaum


Supporting LSF

giving

Dear Friends,

The Life Sciences Foundation (LSF) is a unique institution. Its mission is to record, preserve, and share the history of biotechnology. No other organization is dedicated to carrying out this work.

The history is compelling. Late advances in the life sciences are profoundly transforming the human condition. The technologies are epoch-making, but few in society at large understand the processes of innovation that created them.

LSF is now working to inform the curious public—students, teachers, future innovators, your kids and grandkids, for example—and others with professional interests in the industry, such as journalists, policymakers, and scholars in academic institutions.

The foundation is telling the story in various ways – through events, publications, the Internet, and social media—not for the sake of nostalgia (although there is nothing wrong with that) but for understanding and inspiration. When the past is shared, it becomes a resource for education. If stories aren’t told, experience is squandered.

The LSF staff consists of a small group of historians, archivists, educators, and web designers who are steeped in the history, skilled in heritage preservation, and adept at public outreach. To extend its reach, the foundation has partnered with leading institutions of higher educa-tion and scientific research, including Cold Spring Harbor Laboratory, the National Institutes of Health, the Smithsonian Institution, and the University of California.

I ask you to join me in supporting the Life Sciences Foundation. Please make a gift, or better yet, a three-year pledge. Your donation will help us build a sustainable organization. With your support, we will ensure that the story is told, and told well.

Sincerely,

Carl Feldbaum


Donate OnlineLSF is now able to accept gifts through our website. Giving online is a safe, simple, efficient way to support LSF. Your secure tax-deductible donation will help LSF conduct interviews, collect archival materials, engage key audiences, and tell biotechnology’s story. Go to biotechhistory.org/donate-now to make your gift.

Donate by MailIf you wish to make a contribution by mail, you can send your check to:

Life Sciences Foundation P.O. Box 2130 San Francisco, CA 94126

Gifts of StockDonating stock directly to LSF may be advantageous to you, especially if the stock has increased in value. You will receive an immediate income tax deduction at full value and avoid tax on the gain. LSF will benefit immediately. Contact LSF’s VP for development, Michael Hammerschmidt, by email at [email protected] or call 415.798.2104 for more information.

Honor/Memorial GiftsRecognize the accomplishments of a friend or family member with an honor gift.

Matching GiftsMake your charitable gift go twice as far—it’s easy. Many companies match their employees’ charitable contributions. Some match gifts of spouses or retirees, as well. You can double, and sometimes even triple your impact. Does your firm have a matching gift program?

Corporate and Foundation GrantsEach year, LSF proudly receives support from corporations large and small. Many of the foundation’s programs are sustained by corporate grants. If you make decisions on corporate giving, please consider support for LSF. Many of our supporters direct the giving of individualized funds within national, private, and community foundations, or their own family foundation. This is another way to support LSF.

Planned GiftsPlanned gifts are a very personal way for you to help LSF share the biotech story and achieve your retirement and estate planning goals at the same time. Make LSF a part of your legacy by including a gift of any size in your will or living trust. Sup-plement your retirement income and save taxes while helping LSF with a life income gift. Your gift plan can be tailored to meet your financial situation, now and for years to come. For further information on planned gifts, contact:

Michael Hammerschmidt VP for Development [email protected] 415.798.2104.

Ways to Give to the Life Sciences Foundation


Foundation & Event Updates

LSF news

Foundation Advisors in the NewsMarie Daghlian Joins LSF LSF Staff in the News

LSF advisor and Harvard Uni-versity Franklin L. Ford Re-search Professor in the History of Science, Steven Shapin, was awarded the History of Science Society’s 2014 Sarton Medal for Lifetime Scholarly Achievement. Shapin is one of the world’s most distinguished scholars in the history and sociology of science. He is widely lauded for influential studies of scientific inquiry in historical, cultural, institu-tional, and political context, including Leviathan & The Air Pump, A Social History of Truth, and The Scientific Life: A Moral History of a Late Modern Vocation. The Sarton Medal has been presented annually since 1955 in honor of Harvard’s George Sarton, founder of the journal Isis.

LSF advisor Alan Mendelson was honored with the 2014 Life Sciences Leadership DiNA Award at BayBio’s 11th Annual Pantheon Ceremony held on December 11, 2014. Mendelson served as legal counsel to Amgen for twenty-six years, from 1980 to 2006. Andrea Brown, vice president and corporate counsel at Grifols USA, made the presentation. Lou Lange, founder and CEO of CV Therapeutics from 1992 until the company’s sale to Gilead Sciences in 2009, was also honored. Karen Bernstein, co-founder, chairman, and editor-in-chief of Biocentury Publications, presented Lange’s award. The Pantheon Awards Ceremony celebrates stellar achievements in the Bay Area’s life sciences industry.

LSF welcomes Marie Daghlian to the position of developmental editor. For the past ten years she served as a writer, editor, and researcher for the Burrill Media Group. She helped to produce the Burrill Report and Burrill & Company’s annual industry compendium. Marie brings a wealth of valuable experience to LSF, and will help the foundation’s research, communications, and education teams share the history of biotechnology with multiple audiences, in print and online formats, through multiple outlets. In a former life, Marie designed and manufactured women’s clothing. Her merchandise was sold in boutiques throughout the United States for thirty years.

LSF Research Associate Ramya Rajagopalan published an article in the September 2014 issue of Sociological Theory on the implications of genomics research for understandings of race and ethnicity. The paper was co-authored with leading scholars in biology and the social sciences, including Troy Duster of the University of California, Berkeley and Richard Lewontin of Har-vard University. In October, Rajagopalan was featured on Perpetual Notion Machine, a public radio show produced by WORT-FM in Madison, Wisconsin. The installment, entitled The Genome—Prom-ise and Peril, examined legal and ethical issues created by advances in genomics and personalized medicine. Listen to the podcast at wortfm.org/the-genome-promise-and-peril/


“The Interferon Tournament”

Changing the Face of Biotech Leadership LSF Docent Training LSF has new look

In November, LSF sponsored a special history colloquium hosted by the University of California, San Francisco’s Department of Anthropology, History, and Social Medicine at the university’s Mission Bay campus. Nicholas Rasmussen, professor of history at the University of New South Wales in Sydney, Australia, gave a presentation entitled The Interferon Tournament: Economies of Honor and Credit. The talk reviewed the early 1980s race to clone the interferon gene. Rasmussen is the author of Gene Jockeys: Life Science and the Rise of Biotech Enterprise (Johns Hopkins University Press, 2014). UCSF Professor of Medicine Emeritus Henry Bourne added commentary and led an open discussion.

What does it take to build winning teams over time? Please join us in San Diego on February 12, 2015 for “Changing the Face of Biotech Leadership,” an evening with accomplished industry leaders, women executives who will explore rarely discussed facets of the biotech industry: diversity and the significance of gender in the formation of effective teams and organizational cultures. In the third event of this series, panelists will offer personal insights and recount how they navigated shifting professional landscapes to rise to positions of responsibility. A reception with the speakers will follow. To register, please visit: changethefacesandiego.eventbrite.com.

After a successful run at the Reuben H. Fleet Science Center in San Diego, Genome: Unlocking Life’s Code, a trav-eling museum exhibit created by the National Institutes of Health and the Smithsonian Institution continues its five-year tour of North America. The exhibit will arrive at the Tech Museum in San Jose, California on January 22. LSF is training volunteer docents to introduce museum visitors to the history of genomics and DNA sequencing. If you are interested in sharing the biotech story with people of all ages and wish to volunteer as a docent, please visit Genome: Unlocking Life’s Code at www.biotechhistory.org/genome. After the run in San Jose through April 27, the show will move to St. Louis, Missouri in May and Portland, Oregon in October.

The Life Sciences Foundation has relaunched its website with a new look and new fea-tures. The website is optimized for multiple platforms so you can now explore everything that LSF has to offer on your smartphone just as easily as you would on your desktop. An updated timeline interface allows you to delve deeply into biotech’s rich history and enhanced audio-video capabil-ities help bring that history to life. You can also read the oral histories of biotech pioneers, watch a video of an LSF event on your tablet, or download the latest edition of LSF Magazine. See for yourself by visiting LSF online at biotechhistory.org.


LSF Event Recaps

LSF news

Changing the Face of Biotech Leadership

The Life Sciences Foundation hosted two events this fall that addressed the circumstances of women in the higher circles of the biotech industry. Changing the Face of Biotech Leadership, was held at the Genzyme Center in Cambridge, Massachusetts on October 20, and at Genentech Hall on the Mission Bay campus of the University of California, San Francisco on November 17.

In Cambridge, Genzyme CEO David Meeker welcomed attendees and introduced panel moderator Caren Arnstein, Genzyme’s senior vice president for corporate affairs. The panel featured Deborah Dunsire, CEO of FORUM Pharmaceuticals, Becky Levin, founder and chairman of the executive search firm Levin & Company, Vicki Sato, a professor of management practice at the Harvard Business School and an associate faculty member in the Harvard Department of Molecular and Cell Biology, and Alison Taunton-Rigby, director and trustee of several healthcare, life sciences and financial services organizations.

In San Francisco, Science Futures founder Nola Masterson greeted the audience and introduced panel moderator Simone Fishburn, executive editor of SciBX for BioCentury Publications. The panelists were Gail Maderis, president and CEO of BayBio, Susan Molineaux, president and CEO of Calithera Biosciences, and Kathy Stafford, senior vice president of human resources and organizational development at Solazyme.

In lively discussions, the speakers shared their personal experi-ences as women moving through the industry ranks into positions

of leadership. They dispensed advice on professional development and considered opportunities for women currently entering the field. MassBio was the presenting partner on the East Coast; Bay-Bio was the presenting partner in the West. BioMed Realty Trust, LSF’s national event sponsor, provided generous support for both events. Science Futures was the event sponsor in San Francisco.

A third Changing the Face of Biotech Leadership event will take place in San Diego, in February 2015.

The Cambridge panelists: Vicki Sato, Becky Levin, Alison Taunton-Rigby, Caren Arnstein, and Deborah Dunsire

Nola Masterson of Science Futures (second from right) in San Francisco


Clockwise from bottom left: Kathy Stafford, Gail Maderis, moderator Simone Fishburn and Susan Molineaux

A question for the panel in Cambridge

Deborah Dunsire greets an audience member


LSF news

Cold Spring Harbor Laboratory History Conference: Plasmid Biology

In late September, the Genentech Center at Cold Spring Harbor Laboratory hosted Plasmids: History & Biology, the latest in a series of conferences on the history of molecular biology and biotechnology. The three-day meeting was orga-nized by Jan Witkowski of Cold Spring Harbor Laboratory and leading figures in plasmid research over the past fifty years: Dhruba Chattoraj of the National Cancer Institute, Stan Cohen and Stan Falkow of the Stanford University School of Medicine, Richard Novick of New York University, and Chris Thomas of the University of Birmingham.

The program featured presentations from an illustrious group of geneticists, molecular biologists, microbiologists, and pathologists. Speakers reflected on the development of the field from the discovery of horizontal gene transfer by Joshua Lederberg and Edward Tatum in 1946 to contemporary research with implications for biomedicine, public health, agriculture, ecology, pharmaceutical R&D, synthetic biology, and evolutionary theory. A roundtable on history featured commentary by science historians Roy Curtiss III, of Arizona State University, Matthias Grote, of the Technische Universitat in Berlin, and LSF Director of Research Mark Jones.

Chris ThomasJulian Davies (left) from the University of British Columbia and Richard Novick, New York University

Above: Chris Thomas (left) of the University of Birmingham with Bruce Levin from Emory UniversityLeft: Ananda Chakrabarty of the University of Illinois, Chicago

Other Event Recaps


Left: Stan Cohen and Jim WatsonBelow: The traditional group portrait, at the Hershey Laboratory


Bio-Rad’s Gift

education

The Life Sciences Foundation has teamed with the National Institutes of Health and the Smithsonian Institution to present Genome: Unlocking Life’s Code. Recently, the foundation received a generous donation of educational kits from Bio-Rad Labora-tories in Hercules, California for use in LSF’s museum docent training program.

The kits provide LSF-trained docents with hands-on activities they can use to engage the interested public as they share the wonders of the human genome.

With the Genes in a Bottle kit, for example, museum visitors learn about the double helix as they make necklaces containing samples of their own unique DNA. The Candy Caper and STEM Electrophoresis kits help visitors to understand DNA sequencing as they solve a mystery using the laboratory technique of gel electrophoresis.

Genome: Unlocking Life’s Code was designed by the National Institutes of Health and the Smithsonian Institution to increase public awareness of the ways in which advances in genomics are profoundly reshaping the human experience. The traveling exhibit is currently at the Reuben H. Fleet Science Center in San Diego. It will move to the Tech Museum of Innovation in San Jose for a three-month run beginning on January 22 and closing on April 27, 2015.

BioRad’s DNA Model from the Biotechnology Explorer

educational series


LSF trained docents demonstrate BioRad’s Candy Caper kit to visitors at the Reuben H. Fleet Science Center

R. James Breiding, Swiss Made: The Untold Story Behind Switzerland’s Success (London: Profile Books, 2013).


Winter Reading

biotech bookshelf

It all started with milk. Then came cheese, chocolate, cuckoo clocks, skiing, and a secretive banking system that launders money for corrupt dictators, drug lords, and tax cheats. Author R. James Breiding considers this view of Swiss economic history grievously uninformed and lamentably common. Swiss Made: The Untold Story Behind Switzerland’s Success dispels its miscon-ceptions and aspersions.

Breiding explains that while Switzerland’s dairy products, confections, timepieces, and resorts are world-class, they are not the country’s main outputs, and although fraud is a problem in the Swiss banking industry, it is not a standard business practice. Explanations for Switzerland’s economic success lie elsewhere.

Switzerland is roughly the size of Maryland, landlocked and mountainous, with few natural resources. Its population is just eight million. There are more people in New York City. Because of the nation’s geographic and demographic limitations, Swiss industries are heavily dependent on foreign trade.

Yet, in 2013, the country’s gross domestic product (GDP) per capita was fourth highest in the world: US$74,277. The compara-ble figure in the United States was US$48,377. Switzerland’s great prosperity results from its ability to wring value from cross-bor-der transactions. The banking industry is a prime example. Swiss banks manage an estimated US$7.7 trillion in private wealth from other countries, and generate 11 percent of Switzerland’s gross domestic product.

Breiding speculates that Switzerland’s dependence on outsiders has produced a cosmopolitan culture of openness—to communication, diversity, and free exchange. He sees the attitude reflected in federal law, which protects local autonomy, individual liberty, and economic freedom with light regulation and low tax and tariff rates. The political philosophy is conducive to entrepreneurship and competitiveness.

The book discusses many Swiss industries. Chapter nine is devoted to pharmaceuticals, which in 2012 accounted for 32 percent of the country’s total exports. As a research intensive, in-novation-based sector, the pharmaceutical industry is especially important for Switzerland’s economic future, because it bolsters the nation’s position in the global knowledge economy.

It began in Basel at end of the 19th century when three fami-ly-owned dye and chemical companies, Ciba, Geigy, and Sandoz, began manufacturing medicinal products. F. Hoffman-LaRoche was founded as a dedicated pharmaceutical firm during the same period. Brieding’s narrative follows the origins and growth of these venerable companies through the twentieth century until an unlikely series of events made tiny Switzerland a major player in biotechnology.

In 1990, Roche purchased 60 percent of Genentech for

US$2.1 billion. The following year, it purchased exclusive rights to PCR, Kary Mullis’ revolutionary DNA amplification tech-nology, for US$300 million. In 1994, Ciba-Geigy purchased a 49.9 percent share of the Chiron Corporation for US$2.1 billion, and in 1996, Ares-Serono of Geneva introduced the first of several new recombinant therapeutic products, which enabled it to grow into the world’s third largest biotechnology company.

In 2005, Novartis (formed in the 1996 merger of Ciba-Geigy and Sandoz) acquired all outstanding shares of Chiron for US$5.1 billion. At that moment, three of the world’s ten largest biotechnology companies had Swiss owners. And by 2005, more than seventy new biotech startups had appeared around Basel, Geneva, and Zurich, including Actelion, a company that was founded in 1997, and within seven years had attained a market capitalization in excess of US$2 billion.

The nascent Swiss biotech industry is well positioned for further growth. It is taking shape in the vicinity of large, watch-ful biopharmaceutical and biochemical companies, including Novartis, Roche, Syngenta, and Lonza, and Switzerland’s seven world-class universities—two Swiss Federal Institutes of Tech-nology and the Universities of Basel, Bern, Geneva, Lausanne, and Zurich. Its orientation is global, of necessity. Swiss markets are far too small to permit companies to recoup the massive out-lays required for biopharmaceutical research and development.

Swiss Made is handsomely bound and superbly written. The research base is impressive. Throughout, the survey of Swiss industries is embedded in a rich, contextualizing narrative that describes evolving social, cultural, and political conditions in Switzerland and beyond, over hundreds of years.

Breiding was born in the United States, the son of a Swiss immigrant. He studied in Lausanne, at the International Institute for Management Development. He is not merely an observer of Swiss industry. He is an investor with skin in the game. In 1999, he co-founded Naissance Capital in Zurich.

Florence Wambugu and Daniel Kamanga, eds., Biotechnology in Africa: Emergence, Initiatives, and Future (New York: Springer, 2014).


In 2001, in the midst of a famine, the late Zambian Presi-dent Levy Patrick Mwanawasa rejected food aid from Western countries because it contained genetically modified organisms (GMOs). In 2005, Ghana’s parliament approved biosafety regulations to protect the country’s flora and fauna from harmful GMOs. In 2012, Kenya instituted a ban on GM crops in reaction to a study (soon discredited) that reported tumors in rats fed a diet of GM maize.

Most of Africa’s governments have adopted similar precau-tionary rules. The continent has become a vast battleground on which rival political factions are struggling to decide the future of agricultural biotechnology.

On one side, international organizations including the United Nations’ Food and Agriculture Organization, the United States Agency for International Development, the World Bank, and the Alliance for a Green Revolution in Africa, a partnership between the Rockefeller and Gates Foundations, are seeking to increase food security, eradicate hunger, and reduce poverty through tech-nology investment and development, food aid, and the promotion of science-based regulatory policies.

They have been joined by numerous African stakeholder groups including AfricaBio, Africa Harvest Biotechnology Foundation International, the Economic Union of West African States, and the West and Central African Council for Agricultural Research and Development.

On the other side, environmental groups such as Greenpeace and Friends of the Earth maintain that the introduction of GMOs will lead to environmental degradation, loss of biodiversity, the disappearance of indigenous cultural practices, and the debt subjugation of African farmers to First World governments and corporations.

Their message resonates with African anti-GMO activists and dozens of continental and regional citizens’ groups, including the African Centre for Biosafety, Biowatch, the Coalition for the Protection of African Genetic Heritage, the Malian National Co-ordination of Peasant Organizations, Nyéléni, the Forum for Food Sovereignty, and the South African Freeze Alliance on Genetic Engineering. Some of these groups oppose food aid; some support non-GMO food shipments from the European Union.

Conflicted governments are caught in the middle. To date, GM crops have been introduced for regular use in just four of the continent’s fifty-three countries: Burkina Faso, Egypt, South Africa, and the Sudan.

Biotechnology in Africa is an edited volume that presents argu-ments from the pro-technology side. It was assembled by Kenyan plant pathologist and virologist Florence Wambugu, founder and CEO of Africa Harvest, and Daniel Kamanga, the organization’s director of communications. It includes contributions from lead-ing African authorities—biologists, agriculturalists, economists, policymakers, lawyers, and lobbyists.

The book chronicles the tumultuous history of GM crops on the

continent and reviews technologies currently in development, case studies of successful commercialization, arguments for regulatory reform, and proposals for harmonizing regional biosafety guidelines.

In the opening chapter, Wambugu addresses regional food security and biosafety issues in the context of global political economy. She argues that opposition to GMOs is a greater economic threat to Africa’s smallholder farmers than engineered seeds because under present conditions, only multinational corporations can afford to make technological innovations and improvements in agriculture.

The book then moves to overviews of contemporary biotech research in Africa, including efforts to improve major staple crops such as cassava, potatoes, and bananas.

Later chapters discuss efforts by governments, research institutions, and aid organizations to build infrastructures, train scientists and technicians, and establish trust with citizens and stakeholders.

A key chapter highlights the interrelated technical, economic, political, and cultural dimensions of efforts by African researchers to develop GM sorghum. Sorghum is a primary food source for 300 million people in Africa’s arid and semi-arid regions, but it lacks essential micronutrients, such as vitamin A, and its iron and zinc content is not in a bioavailable form. Because sorghum is a dietary staple, these deficiencies can have serious health conse-quences, such as xerophthalmia, which causes blindness, anemia, and diarrheal disease.

The African Biofortified Sorghum Project, a consortium of fourteen public, private, and non-profit organizations, is working to increase the nutritional value of varieties preferred by African farmers while ensuring biosafety and environmental protections. Field trials have taken place in Kenya and Nigeria, but resistance to the technology and a lack of sustained funding has put the project at risk.

Biotechnology in Africa has certain stylistic and structural faults (non-specialists will find the material informative but dry; specialists will be disappointed by the lack of an index), but the book’s message is plain: without substantial investment, effective community outreach, and consistent governmental support, potentially beneficial technologies will continue to languish.


Dennis Gillings

oral history spotlights

Dennis Gillings has always been a risk taker. In 1982, he gave up a secure career as a professor at a top university to build Quintiles, the biostatistical consulting company he had cofounded with a university colleague. The company was born from the idea that drug development is, in essence, an information science, and that patients benefit when all stakeholders are properly informed. Having grown Quintiles from a tiny startup to a publicly traded transnational corporation, an industry leader with operations in fifty countries, Gillings risked it all once more by taking the company back into private ownership...

Dennis Gillings was good at math—always at the top of his class. He earned a bachelor’s degree in mathematics at Exeter, a diploma in mathematical statistics at Cambridge, and then a PhD in mathematics at Exeter in 1972. His advisor, John Ash-ford, steered him into biostatistics and health services modeling. “Ashford made a tour of the United States,” Gillings says. “He came back and told me biostatistics was a big thing, and there was a shortage of people trained in the field.”

Ashford encouraged his protégé to consider a faculty position in biostatistics in the School of Public Health at the University of North Carolina (UNC). Gillings traveled to a biometrics meeting in Germany to meet the chair of the department, Bernard Greenberg. Greenberg wanted someone to run the unit’s health services program, and to start right away. He offered Gillings the job on the spot.

But Gillings had made plans for extensive travel in Africa, and didn’t want to give them up. He took one of his first risks when he asked for a one-year deferment. He got six months. “A typical business negotiation,” he says. With little more than a suitcase and sense of adventure, he drove from Morocco to South Africa. Gillings calls the journey “an extraordinary, character-forming experience.”

He immediately embarked on another life-changing experi-ence when he flew to North Carolina. Gillings had grown up in London imagining that America was a dynamic and progressive place. Chapel Hill didn’t fit his mental picture: “I had assumed that because of the country’s material wealth, it would be more sophisticated, but it wasn’t. In North Carolina, there were “blue laws” that restricted liquor sales, a hangover from Prohibition, I suppose. Wine was almost unheard of and a lot of the gourmet foods I was accustomed to were unobtainable.”

Gillings began his appointment in a small trailer in the woods

adjacent to the university, Trailer 39. At first he was put off by the arrangement, but he soon found that separation from the main campus had advantages: “My colleague, Gary Koch, an outstand-ing statistician, had decided to relocate there. We built our own little empire with our own students. We had a good time there, professionally and socially.”

As associate director of the Center for Health Services Research at UNC, Gillings provided statistical consulting services for the entire health sciences campus, which included the schools of med-icine, pharmacy, nursing, dentistry, and public health. At the time, graduate students provided labor, but weren’t compensated. One of Gillings’ first acts was to change this plan: “It had a huge impact because we used to get a large number of what I called ‘rubbish questions.’ People clearly hadn’t thought through what they want-ed. As soon as they had to pay $25 an hour, their ability to describe and think through what they wanted improved enormously.”

Gary Koch soon recommended Gillings’ services to Ken Falter, the chief clinical statistician at the large drug maker, Hoechst-Roussel. Falter wanted help interpreting adverse effects of a diabetes drug called Glyburide. The problems had been reported in Germany. Gillings had all of the charts and reports translated from German by colleagues in the languages department, and then determined that the drug was being

Oral histories are narrative accounts of events and historical processes as told from the point of view of eyewitnesses and participants. They pre-serve the experiences, recollections, and testimonies of history-makers.

Calculated Risk and Reward


prescribed, in some cases, to the wrong patients. The finding prompted Hoechst-Roussel to change the drug’s label, which led to regulatory approval of an important new treatment in the United States.

The problem was solved in a month, and the good result snowballed into many more industry assignments. Gillings and Koch’s statistical services were soon in high demand. Gillings proposed the creation of a non-profit institute within the University through which revenues from contract research would be funneled back to the school. The UNC administration rejected the idea. Gillings decided to start his own firm. It was permissible—university rules allowed faculty members to devote one day per week to outside consulting.

The new enterprise was called Quintiles. It was housed originally in Trailer 39, “and that worked very well,” Gillings says. “I would feed a lot of the work into projects for students. Papers would get published, and the students generated con-sulting income.” The business grew. In February 1982, Gillings incorporated and moved the firm off campus with five full-time employees.

As Quintiles continued to expand, Gillings felt pulled to devote more time to the company. He was by now a full pro-fessor at the university, but in certain respects the achievement felt limiting. He started to entertain the notion of leaving: “I thought, ‘If I stay here for the rest of my life, there’s too much more of the same.’” Seeing business as “the best of both worlds,” he took a two-year leave of absence in 1986 to focus full-time on Quintiles. It was another calculated risk. He reckoned that he could go back to higher education if things didn’t work out.

It was a perfect time to grow the business. Drug makers had begun outsourcing clinical development work in the 1980s in order to rein in skyrocketing R&D costs. Quintiles started with statistical analysis, added data management, and soon offered a comprehensive clinical services package. “By about the late 1980s, I’d really built that model very successfully and built it internation-ally,” Gillings says. He had moved the company into England, with clinical trial management operations in London and Reading.

By 1990, it was clear that the way forward was to address the full range of drug makers’ clinical needs, and to do it efficiently by standardizing clinical research. Gillings moved to reorder the field through the introduction of new information technologies, but struggled against regulatory and industrial inertia. Comput-er systems couldn’t be changed in the middle of clinical studies without the approval of the FDA, and clients dragged their heels.

Earnings demands from Wall Street soon tempered much of the resistance. Quintiles prospered and extended its reach into Europe, Asia, and Australia through acquisitions and new invest-ments in infrastructure. In 1994, in order to fuel further growth,

Gillings sought to raise money in public markets.During the grueling roadshow in advance of the IPO, he told

prospective investors that the pharmaceutical industry didn’t have the internal resources to move all of its products to market, and that helping them represented an enormous opportunity. “There were a lot of drugs in the pipeline,” he says. “It was a once-in-a-lifetime growth spurt for the pharmaceutical indus-try.” Quintiles successfully completed the IPO.

The company became a global full-service contract research organization (CRO), handling not only clinical trial man-agement, but also marketing and sales functions, and health economics policy analysis. In 1998, the company’s revenues exceeded $1 billion.

Gillings realized that although the opportunity was global, success depended on local performance. When opening new branches, he made visits, met with regulators, scientists, and customers, and evaluated each opportunity on the ground. He also took quarterly worldwide tours of company facilities to meet face-to-face with employees at every site.

Having no formal training in business, Gillings credits his success to his evaluation skills and his intuitive understanding of statistics: “I have been quite good at taking difficult problems and transforming them into something manageable.” His ability to derive useful information from confounding data sets has enabled him to make sound calculations of risks and rewards.

It wasn’t always easy. In 2003, Gillings decided to take Quin-tiles back to private ownership—he didn’t want the organization to be driven by short-term expectations as it retooled for the future. At risk was his entire stake in the company he had started in Trailer 39 and grown into a thriving transnational corporation operating in fifty countries.

Once again, the gamble paid off. Gillings was able to improve Quintiles’ infrastructure, processes, and strategic flexibility. The retrofitting drove accelerated growth over the next ten years. In May 2013, Quintiles went public again on the New York Stock Exchange, under the symbol Q.

Gillings has observed the CRO sector evolve from a con-sulting resource in the 1980s, to an outsourcing resource in the 1990s, to an indispensable strategic infrastructure in the 2000s. “Now that we serve a strategic function,” says Gillings, “we are changing the way things are done. This is as it should be, because we have become highly skilled in the logistics of drug develop-ment. If you took CROs out of the current system, nothing much would get done.”

With promising scientific, therapeutic and analytical advanc-es on the horizon, Gillings now anticipates the richest reward of all flowing from his calculated risks—better health for patients around the world.


George Poste

oral history spotlights

George Poste is a big picture guy. He believes that progress in sci-ence and medicine requires understandings of complex wholes, and that reductionism is foolhardy. “With reductionism,” he says, “you delude yourself into thinking that you can understand a complex system by analyzing its parts, but you can’t.” Poste’s appreciation for big picture thinking has been reinforced by adventures in cancer research, drug discovery, genomics, and biosecurity, but it first came to him through exposure to the traditional practices of an older world.

George Poste grew up in rural Sussex, in the south of England, during the postwar period, a time of austerity and reconstruc-tion. The life of the local community was ordered by the natural rhythms of farming. His father was a mechanic, “a keen practical intellect” who made his living servicing farm machinery and vehicles.

Poste observed that veterinarians also played critically important roles in the farm economy, and in the course of their work confronted “a diverse set of intellectual challenges.” Veterinarians are trained to diagnose and treat ailments of many different kinds—equine, bovine, porcine, ovine, caprine, and so on. It seemed to the boy that their practice was far more demand-ing than that of the village physician.

In 1954, Poste came to a branching point—the Eleven Plus exam that stratified primary school students on the basis of intellectual ability. He took the exam a year early, but still scored in the top 5 percent, which put him on the university track. Some time later, he began accompanying local veterinarians on their rounds. He wanted to acquire their big picture perspective on health and illness.

At the age of eighteen, he went off to the University of Bristol with a plan to study clinical veterinary medicine. He was not sur-prised to find that “veterinary students had the highest entrance qualifications, and the medics, dentists, and vets all went to the same classes.”

At the time, biomedicine was being rebuilt on molecular foundations. Poste feels “fortunate to have been there at the beginning, to get training in molecular biology.” He became particularly interested in cancer—studies of retroviruses and oncogenes had begun to reveal the complexities of tumor biology.

Poste completed his veterinary training in 1966, but rather than going into clinical practice, he went on to earn a PhD in

virology at Bristol in 1969. He then accepted a position as a lecturer in the field at the University of London’s Royal Postgrad-uate Medical School.

Two years later, he took a sabbatical at the Roswell Park Cancer Institute in Buffalo, New York. “I’m the only guy who ever went to Buffalo not knowing that it snows there,” he laughs. The institute had recruited a stellar multidisciplinary group composed of molecular geneticists, cell biologists, immunolo-gists, and pharmacologists. Poste found it a uniquely stimulating environment: “There was a great intellectual nucleus and I was trying to absorb everything like a sponge.” The sabbatical visit turned into a permanent tenured appointment at the State University of New York.

Then, out of the blue in 1981, Poste received a call from a headhunter representing a “major research firm.” It turned out to be the Philadelphia pharmaceutical house, Smith, Kline & French. “I had never thought about going into industry,” says Poste. “I had a typically insular, academic view of the world, and by this time I was a full professor. But I went through the inter-views, and only an idiot would come away unimpressed by what I saw and the ambitious plans that the company had to participate in the then emerging new domain of biotechnology.”

SmithKline had recently introduced the world’s first

Embracing Complexity


blockbuster drug, the anti-ulcer histamine blocker cimetidine (Tagamet), one of the inventive payoffs of James Black’s pioneer-ing work in “rational drug design.” Bryce Douglas, the company’s senior vice president of R&D, recognized the potential of molecular biology to advance this novel mode of drug discovery and development. He encouraged Chairman Henry Wendt and CEO Bob Dee to invest heavily.

Douglas recruited Stanley Crooke, who had built Bristol- Myers Squibb’s oncology program, as president of R&D, and Poste as vice president of research—two people he believed had the background and the will to innovate. “This was sophisticated strategic planning,” says Poste. “The molecular revolution was underway, and Bryce wanted SmithKline to be part of it.”

Still, it was a struggle to bring molecular biology into an orga-nization steeped in pharmaceutical chemistry. Poste remembers: “It was a pretty traumatic time. Stan Crooke and I literally tore the place apart. We imposed radical change.” And, he admits, “It wasn’t always done optimally or with adequate consideration.” It was a difficult time for the company’s powerful marketing group, too. “Sales people understand existing markets,” says Poste, “but they have a harder time with disruptive technologies.”

Battles ensued. Poste was convinced, for example, that recombinant DNA technology would revitalize SmithKline’s vaccine business, but on three separate occasions, factions in the company’s executive suite pushed to sell it off. “I laid down in front of it each time,” says Poste, “and I’ve got the scars on my back to prove it. But I was right—vaccines now have profit margins that equal pharmaceuticals.”

Crooke left in 1988 to start his own company, Isis Pharmaceu-ticals, and Poste took over as president of the R&D division. In the 1990s, as part of a forward-looking executive cadre, he helped to devise a “grand plan” for the company. It was an early vision of “personalized medicine.” Poste anticipated an integrated program of genomics-based drug discovery, companion diagnostics, and healthcare informatics.

In 1993, he spearheaded SmithKline’s landmark $125 million deal for rights to develop drugs, vaccines, and diagnostics from gene sequences identified by the pioneering genomics company, Human Genome Sciences. It was a bold move. The company recouped its investment by subleasing access to the sequence data, but the integrated healthcare framework wasn’t realized. “It was premature,” says Poste, “and the company reverted back to the standard pharma model.”

In retrospect, Poste sees the episode as a lesson in biological complexity and big picture pharmacology: “You need to work from the bottom up, you need the genes, but you also need a top-down understanding of the system. So, we missed a lot of things.” Two decades later, molecular medicine is still moving into terra incognita. The “personalization” of medicine is still in its infancy.

In 2000, SmithKline merged with Glaxo Wellcome, and Poste was ready to step out. He had by this time received high honors from his country of origin—he had been elected a Fellow of the Royal Society and received the Order of Commander of the Brit-ish Empire from Queen Elizabeth—and he had helped shepherd more than thirty new drugs to market.

In his “retirement,” Poste planned to shuttle between his three favorite cities—San Francisco, San Diego, and Scottsdale, Arizona—serving biotech enterprises as a director and consul-tant. After 9/11, however, his expertise became vital to the US Department of Defense. For two years, he traveled regularly to Washington, DC to chair the agency’s Defense Science Board Bioterrorism Task Force (and he continues to advise on matters of national security).

In 2003, Michael Crow, president of Arizona State University, asked Poste to help the school set up a life sciences innovation center, the Biodesign Institute, that would merge the best of university and industry research styles. Some on campus felt the two approaches were antithetical. Poste didn’t. He accepted the invitation.

He implemented what he calls a “3M” approach as the core organizing principle in the Biodesign Institute’s multi-investiga-tor, multi-institution, multi-million dollar research projects. “Just as in industry,” Poste explains, “projects are led by teams and the matrices of ever-fluid, ever-shifting assemblies of skills needed at any given time to tackle specific problems.”

In 2009, Crow asked Poste to lead another new program, the Complex Adaptive Systems Initiative (CASI), to drive 3M proj-ects on a larger scale across the university’s research units. CASI seeks multidisciplinary solutions to pressing problems as they emerge from within complex sociotechnical systems—financial crises, food and water shortages, pandemics, bioterrorism, cyber warfare, and the complex potential effects of climate change, for example. For a big picture guy, CASI is an ideal environment.

Poste chalks up much of his professional success to luck, and the fact that he never worked for anyone who viewed him as a competitor: “Every single person I‘ve worked for has been gifted. None felt threatened by my talents.” He also acknowledges the stimulating influence of creative and insightful colleagues at Bristol, Roswell Park, SmithKline, and Arizona State.

Beyond good fortune and good friends, he recognizes the importance of three fateful personal decisions: “To go to univer-sity, to come to the United States, and to go into industry. Those choices led me to a very enjoyable and successful life.” Finally, Poste cites his natural inquisitiveness, inherited from both of his parents. “I still have a voracious appetite for knowledge,” he says. “My kids joke that when they try to nail the coffin shut, my hand will shoot out and they’ll hear, ‘Wait a minute, there’s one more thing I want to know.”


The First Hambrecht & Quist Healthcare Conference

gems from the archive

It seemed positively balmy to those who had traveled from the East Coast for the first Hambrecht & Quist (H&Q) Healthcare Con-ference, a three-day meeting of investors, stock analysts, bankers, and company executives at the St. Francis Hotel, pictured above, on San Francisco’s Union Square. Two hundred and twenty registered attendees were on hand to take the measure of the healthcare indus-try in the West and learn about new opportunities in biotechnology.

Presenting companies included hospital operators, medical device manufacturers, a medical information services provider, and five biotechnology startup firms: Centocor, Collagen, Genentech, Monoclonal Antibodies, Inc., and Xoma. The biotech industry was still very small. By 1983, it had put just a handful of products on the market, a few diagnostic kits and one therapeutic—recombinant human insulin, invented by Genentech and manufactured and marketed by Eli Lilly and Company.

The meeting was organized by Annette Campbell-White, H&Q’s healthcare specialist. As new biotech and medical device companies proliferated in the Bay Area and became increasingly visible on Wall Street, she had the notion that H&Q could host a West Coast event to complement the annual East Coast healthcare conference held by Alex. Brown & Sons in Baltimore, Maryland.

Monday’s discussions focused on trends in healthcare delivery,

regulation, and pricing. On the second morning, a ninety-minute session posed a question, “Medical Genetics – the Next Revolution in Medical Therapeutics?” Panelists Mr. Michael A. Wall, president of Centocor, Inc., Dr. Patrick J. Scannon, president of Xoma, Inc., and Mr. R. Swanson, president of Genentech, Inc., talked about new opportunities in pharmaceuticals and diagnostics created by the invention and application of recombinant DNA and hybridoma technologies.

The conference was roundly deemed a success. A second was held the following year, and it turned into an annual event. In 1999, Hambrecht & Quist was acquired by Chase Manhattan. The event was renamed the Chase H&Q Healthcare Conference. Chase merged with J.P. Morgan in 2000, and from 2003 on, the meeting became known by its current name, the J.P. Morgan Healthcare Conference.

The event has grown tremendously over the years. Last year, more than 430 public and private companies presented to more than 9,000 invited guests. J.P. Morgan hosts many investor events every year. The January Healthcare Conference in San Francisco is the largest.

Campbell-White attributes the popularity of the conference to scheduling and the weather: “I believe to this day that the key to the success of the conference is timing. People have new budgets and new ideas and the weather’s bad on the East Coast.”

Monday, January 10, 1983. High temperature: 54° F.


obituary

Robert Schimke enjoyed an illustrious thirty-five year career in science at the National Institutes of Health and Stanford University. He established the field of protein turnover, advanced understandings of the ways in which hormones control gene expression, elucidated the phenomenon of gene amplification, and showed how apoptosis (programmed cell death) prevents genomic instabilities associated with cancer. Schimke mentored many stu-dents who later made important contributions to the life sciences, biomedicine, and the biotechnology industry, and he played a brief but consequential role in the formation of Amgen. After a serious injury in 1995 made it impossible for him to run his laboratory, he devoted his energies to another creative pursuit—painting.

Robert Schimke was born and raised in Spokane, Washington in the years spanning the Great Depression and World War II. His father was a dentist, his mother a piano teacher. Schimke didn’t remember his youth with fondness. He was a gifted stu-dent, but also, in his words, “a holy terror” with a penchant for finding trouble. Still, he managed to earn a full scholarship for early admission to Stanford University, which made him exempt from military conscription.

He majored in biology, graduated in 1954, a year early, and entered the Stanford School of Medicine. There, he benefitted from a new program designed by Dean Robert Alway and Henry Kaplan, chair of the radiology department, to modernize the curriculum and introduce medical students to laboratory research. Schimke joined the laboratory of pharmacologist Avram Goldstein, and worked on the biochemistry of addiction. He further developed his research skills as a postdoc in the laboratory of noted biochemist Oliver Lowry at the University of Washington, St. Louis.

After an internship at Massachusetts General Hospital, Schimke joined the NIH in 1960. He worked in biochemical pharmacology at the National Institute of Arthritis and Metabol-ic Diseases and studied the cellular regulation of enzymes under the direction of Herbert Tabor. Researchers knew that substrates stimulate enzymatic activity; Schimke investigated the role of substrates in enzyme degradation.

He coauthored a 1964 paper on the topic that received hun-dreds of citations and established enzyme stabilization as a new field in biochemistry. He discovered that enzymes are protected from degradation when bound to their substrates, the molecules on which they act.

In 1966, Schimke returned to Stanford to teach in the School of Medicine’s Department of Pharmacology. He served as chair from 1970 to 1973, and then moved into the university’s Division of Biological Sciences. He built on his protein turn-over discoveries and focused on the hormonal control of gene regulation. He demonstrated, first in rat livers and then in chick oviducts, that specific gene functions could be influenced by steroid hormones.

In 1978, Schimke and graduate student Fred Alt showed how murine sarcoma cells developed resistance to the cancer

Robert Tod Schimke (1932-2014)

Schimke’s work on gene amplification was critical to the production of recombinant erythropoietin (EPO), an important turning point in the history of the biotechnology industry.


drug methotrexate. Methotrexate works by inhibiting an essential enzyme. Schimke and Alt found that cells responded by increasing, or “amplifying,” the number of copies and expression level of the gene that codes for the enzyme. Beyond explaining a mechanism of drug resistance, the work revealed a high degree of genomic instability in cancer cells.

In the fall of 1979, Schimke happened to sit next to venture capitalist Sam Wohlstadter on an airplane. Wohlstadter was then working with colleague Bill Bowes to identify opportunities for starting new biotechnology companies. Schimke and Wohlstadter discussed gene splicing. Wohlstadter told Bowes about his new Stanford connection, and the pair approached Schimke about forming a new venture.

Schimke declined the invitation to become a founder, but agreed to serve as a scientific consultant. He was soon forced to bow out of the project, however, when his father became gravely ill. He suggested that Bowes and Wohlstadter contact UCLA biologist Winston Salser, whom he knew to be highly entrepreneurial. Salser became a cofounder, recruited an all-star scientific advisory board, and, with Bowes, gave the company a name, Applied Molecular Genetics—Amgen, for short.

Schimke eventually joined the company’s scientific advisory board and his work on gene amplification became the basis for techniques that Amgen employed to scale up production of its first product, recombinant erythropoietin (EPO). Around the same time, Chris Simonsen left a postdoctoral position in Schimke’s Stan-ford lab and found employment at Genentech, where he helped Art Levinson develop a similar method for amplifying the expression of the gene for tissue plasmin-ogen activator (tPA). The development and introduction of EPO and tPA were important turning points in the early history of the biotechnology industry.

Schimke continued to investigate the underlying mechanisms of gene amplification through the mid-1980s, and then turned his attention to cell-cycle events and apoptosis. Schimke showed that selective pressures on cells when cell-cycle events were inter-rupted were important factors in inducing the genomic instability that had already been shown at work in gene

amplification.Tragedy struck in 1995. Schimke, an avid cyclist, was

severely injured in a collision with a car while cycling home from his lab. He was partially paralyzed from the neck down. With determination and years of physical therapy, he regained some mobility, but remained mostly wheelchair bound for the rest of his life.

The accident effectively ended Schimke’s scientific career at age sixty-two, but he had already considered retiring to spend more time painting and gardening. For a time, he kept abreast of scientific progress as an associate editor for the Journal of Biological Chemistry, but by 2002, his time was wholly devoted to painting. He experimented prolifically with different styles and media. Unable to enjoy his previously active lifestyle, he told an interviewer that he invested his energy in his paintings: “They are all moving. There’s nothing static about them.”

In nearly thirty years at Stanford, Schimke mentored more than one hundred students, many of whom went on to have distinguished research careers in academia and industry. Many have expressed admiration and appreciation for his direct style of communication, his passion for teaching, and his ability to anticipate move-ments in scientific research. Fred Alt, now a professor of genetics at Harvard Medical School and a Howard Hughes Medical Institute investigator, says, “He was incredibly honest. He would say exactly what he thought about your work, and he was usually right. As a mentor, he was tough, but never impatient.”

Robert Schimke died on September 6, 2014 in Palo Alto, at the age of eighty-one. He is survived by his wife Patricia Jones, a professor of biology at Stanford, three daughters, and five grandchildren.

Robert Schimke painted in a variety of styles and media, but all of his works were kinetic. “They are all moving,” he said. “There is nothing static about them.”


Florence Wambugu On Agriculture and Food Security in Africa

Florence Wambugu grew up in the foothills of Mount Kenya in the 1950s and 1960s. Food was scarce. The local staple crop, the sweet potato, was frequently ravaged by blight. Wambugu resolved to do something about it. She became a plant pathologist. She studied at the University of Nairobi and went to work for the Kenyan Agricul-tural Research Institute. She concurrently obtained a master’s degree at North Dakota State University, and earned a PhD at the University of Bath, in England. In 2002, she founded Africa Harvest Biotech Foundation International, an organization devoted to technological and economic progress in all of the continent’s diverse regions. Here Wambu-gu talks with LSF’s Brian Dick about opportunities and challenges related to the adoption of agricul-tural biotechnologies in Africa.

BD: Dr. Wambugu, you are an advocate for the use of agricultural biotechnologies to increase food production in Africa. What led you to this pursuit?

FW: Food security is a serious problem in Africa. The genetic modification of plants can help to solve it. As a PhD student, my thesis research focused on controlling the sweet potato virus that was limiting yields. Viral diseases often devastate African crops. There’s no winter to break the disease cycle so the incidence of infection is very high. Plant diseases are also spread by cultural practices that farmers are reluctant to give up, such as sharing seeds and cuttings. Genetic modification (GM) technology could potentially confer resistance to viral infection and increase yields, allowing farmers to continue sharing seeds. That’s what originally attracted

me to genetic engineering. After a brief period of postdoctoral work in the United States, I came back to Africa.

BD: Please tell us about Africa Harvest. What are the organization’s goals and current projects?

FW: Our mission is to improve food security and the welfare of African populations by using the tools of agronomy and agricultural biotechnology. We are working to build healthy communities and help smallholder farmers produce plentiful, nutritious food supplies. We must support producers. We are not disseminating information and deploying technologies simply to get better field results. We are working to create sustainable agricultural systems.

We bring a comprehensive value-chain approach that provides farmers with access to high quality seed, information, and material resources—through microcredit programs, for example. We must fight poverty as well as insects, plant blight, and environmental problems. It is absolutely crucial that smallholder farmers have access to functional markets. They have to be able to sell their goods. Toward this end, Africa Harvest conducts economic research, lobbies for constructive policy change, and identifies opportunities for establishing produce market centers. We know that technology uptake is high when there are robust markets in place.

Dr. Florence Wambugu at a meeting sponsored by the World Agroforestry Centre

in conversation


BD: You’re describing a holistic approach.

FW: Yes, we work on natural resource management, for instance. Africa is dealing with many different kinds of environmental problems—desertification, water pollution, loss of biodiversity, and the effects of climate change, for example. All present major challenges, especially to poor rural people who depend on natural resources for their livelihoods. Africa Harvest engages with communities to improve the quality of water and soils, conserve forests and biodiversity, and implement climate change mitigation strategies.

Incidentally, Africa Harvest has yet to deploy GM technology. So far, the products are cultivars improved by conventional means, such as disease-free, high-yielding tissue-culture banana plantlets. Sixty percent of Africa Harvest’s work is doing the legwork to increase farmers’ access to hybrid seeds and plants. There is still significant resistance in Africa to the introduction of GM crops.

Our communications programs are focused on disseminating accurate, reliable information about GM technologies in order to counter the influence of anti-GM scare campaigns, and to dispel public confusion. At the same time, we are working to develop partnerships with farmers’ associations, governments, and food aid organizations. Africa is a big continent. If we can effectively share with others what we’ve learned, we will make an impact.

BD: In what specific areas can biotechnologies be brought to bear on economic and food supply problems?

FW: There are many. GM cotton represents a big economic opportunity for Africa. Kenya’s once-flourishing cotton industry has been decimated by the high cost of pesticides, most of which are imported. Farmers ended up spending most of their income on chemicals. In India and South Africa where GM cotton is approved for planting, small-scale farmers are benefitting much more than large-scale farmers because the new technology allows them to use much less pesticide on their cotton crops.

The introduction of GM seeds could dramatically improve maize production in Africa. The average yield of maize in Africa is about two tons per hectare, one-fifth the average yield in North America. Many African farmers keep their seeds for replanting rather than buying them anew every season. This practice spreads disease, and accounts for a large percentage of yield loss. Insects are a major problem, too. They are vectors for transmitting diseases to plants. We could double yields by plant-ing maize genetically modified to express the Bt trait for insect resistance. In addition, incorporating the technology into the seed simplifies the diffusion process. Farmers already know how to handle seeds, so they can readily benefit from the technology without radically altering their way of life.

BD: The development of a genetically modified sweet potato was your first project, but it failed in field trials in 2004. What are the prospects for reviving it?

FW: As I said, I focused on the sweet potato because it was heavily infected and because warm winters provided no way to break the infection cycle. We explored vaccinating against aphid-borne viruses so farmers could continue to share seeds. The first field trial failed to confer durable resistance because the virus infecting sweet potato plants in Africa was more virulent than the strain we used to modify the plant, which came from a clone being tested at the University of North Carolina. Unfortunately, we couldn’t continue the research because funding dried up. Research to develop an effective vaccine against the sweet potato virus continues in Uganda. It is related to my earlier work, but I’m not personally involved in the follow-up. In any case, the history of the sweet potato project illustrates some of the obstacles confronting African researchers.

BD: Are there points of light? Current projects with promise?

FW: There are. Africa Harvest is currently working with Pioneer,

Africa Harvest uses tissue culture technologies to improve banana yields


a DuPont company, on the biofortification of sorghum. It is similar to the Golden Rice project. We are trying to enhance nutritional value. We have genetically modified the plant to increase its vitamin A content. This is important because communities in the driest parts of Africa rely on sorghum as a staple crop since it is drought-resistant. But because sorghum lacks essential micronutrients, people in these communities can suffer from blindness caused by vitamin A deficiency, or anemia due to a lack of iron. There is a dedicated website for the Africa Biofortified Sorghum Project: biosorghum.org. The project was started with funding from the Bill and Melinda Gates Founda-tion. Further funding from the Howard G. Buffett Foundation supported advanced technology development.

BD: Your book, Biotechnology in Africa, discusses the response of African governments to the potential uses of GM technology. What are some of the challenges and prospects?

FW: A lot of money is being poured into research in Africa, but disseminating that research to farmers is very poorly funded. African farming is small-scale. Growers need to be educated and nurtured. They need guidance. Without addressing these needs, it will be very hard to make improvements in African agriculture, no matter how much money is spent on research. This has been my main punch line for some time: we need to expand financial support for technology diffusion. We need to reach out effectively to farmers and local communities. From a distance it may seem otherwise, but most African countries have publicly funded biotechnology laboratories. The science is not the problem. Rather, it is a lack of investment, and more importantly, a lack of understanding regarding the complexity of getting GM products to market, mainly due to the high cost of the regulatory process. African universities are doing good work, but they are constrained by the great expense of compliance with national and international regulatory requirements.

Overcoming the pervasive influence of anti-GM activism is

another big challenge. Anti-GM groups are hampering progress by propagating fear. They claim that GM seeds are instruments of imperialism and corporate control. They say that big multi-national companies want to control the seed because it enables them to dominate Africa by economic and technological means. They also continue to recycle discredited studies that purport to show evidence of harm caused by genetically modified products—severe allergic reactions, cancers, and autoimmune disorders. Many politicians are captive to this kind of fear mongering. It is true here in Kenya. GM food imports have been banned in this country. This is unfortunate because government support is critical if the continent is to benefit from GM technol-ogy. Without political will, you can’t commercialize a product in Africa. GMOs are so highly politicized that the science or technology alone is not sufficient.

BD: You mentioned the high costs of regulatory approvals. Have they effectively barred public institutions from introduc-ing beneficial technologies?

FW: Yes, but the door is not entirely closed. Four African countries have approved GM crops: Burkina Faso, Sudan, South Africa, and Egypt. Many others are putting reasonable regula-tory frameworks in place. The Sudan, for instance, has gotten up to speed very quickly with GM technology from China. In addition, young Africans are gaining knowledge through the Internet. They are becoming more sophisticated. A critical mass is forming. I believe that the next generation of politicians assuming power in Africa will be more open to new technolo-gies. So there’s hope for the future. African biotechnologies are coming of age. We’ve made a big investment, and I believe it will come to fruition.

BD: Thank you, Dr. Wambugu.

FW: My pleasure, Brian, thank you.

Sorghum is an important African staple. Africa Harvest is developing a biofortified variety.


S ingapore became a sovereign democratic state when it withdrew from the Republic of Malaysia in 1965. Over the next two decades, free trade policies, a low debt burden, and export-oriented industries trans-formed the national economy into a dynamic high

growth Asian “tiger.”

The city-state’s prosperity has been sustained into the twen-ty-first century, thanks in part to public and private commitments to participation in the emerging global knowledge economy. Philip Yeo can take some credit for it. A PhD systems engineer with a Harvard MBA, Yeo was appointed chairman of Singapore’s Economic Development Board in 1986. He became one of the chief architects of national economic policy.

Yeo pressed the government to dedicate human, intellectual, and material resources to high tech innovation. In 2000, he became the founding chairman of Singapore’s Agency for Science, Technology, and Research (A*STAR), and adopted projects in the life sciences and biotechnology to showcase Singapore’s innovative capacities.

With a budget of US$1.15 billion, Yeo implemented the Biomedical Sciences Initiative (BMSI), an ambitious plan to foster academic-industry collaborations. The mission was to establish Singapore as a global leader in healthcare delivery, biomedical innovation, and biopharmaceutical outsourcing services. The initiative gave rise to Biopolis, a science park designed to help Singaporean scientists and industrial partners meet or exceed global standards of excellence in research, product development, manufacturing, and clinical testing.

Nobel laureate Sydney Brenner coined the name. He was impressed with Singapore’s commitment to science, and taken by Yeo’s notion of a bio-city. He was eager to serve as a consultant: “This was to be an experiment in developing state-of the-art biomedical research at a national level in what was a third world country not too many years before. I viewed it as an exciting venture and an exciting opportunity.”

Yeo located Biopolis near the National University of Singapore.

He explained that “the close proximity of talent from corporate laboratories, startups, and public research institutes will create a vibrant R&D environment to spur new discoveries and speed their translation into applications.” He made a concerted effort to attract world-class scientific talent. Edison Liu, former head of clinical sciences at the US National Cancer Institute, was his first five-star recruit. Others followed.

Biopolis: Singapore’s Scientific TigerAn ambitious plan to foster public-private R&D collaboration

Left: Philip Yeo was the founding chairman of Singapore’s Agency for Science, Technology, and Research (A*STAR)

Global Biotech Centers


The first phase of construction at Biopolis raised seven buildings at a cost of US$290 million. The 600,000 square foot complex was completed in 2003. Five of the structures housed A*STAR research institutes—the Bioinformatics Institute, the Bioprocessing Technology Institute, the Genome Institute, the Institute of Bioengineering and Nanotechnology, and the Institute of Molecular and Cell Biology. The institutes employed more than 2,000 state science workers. The two other buildings provided laboratory and office space to private companies.

Multinational pharmaceutical corporations arrived to lease space and set up operations. Eli Lilly and Company was the first. GlaxoSmithKline (GSK) and Novartis soon followed. Lilly opened a systems biology laboratory, GSK established a center for research on cognitive and neurodegenerative disorders, and Novartis created an institute for research on tropical diseases. Each addition was an important validation of Yeo’s vision.

Investments in Biopolis returned early dividends when an out-break of severe acute respiratory syndrome (SARS), a potentially deadly viral illness, originated in China and spread into Southeast Asia. In March of 2003, the virus arrived in Singapore and tested the city-state’s public health system. Two hundred eighty-three persons were infected. Thirty-three died.

It could have been much worse had not teams of scientists at Biopolis’ Genome Institute worked in collaboration with private

firms, Roche and Genelabs, to develop a rapid immunodiagnostic test. Singaporean authorities used the product to identify and isolate infected patients, and slow the spread of the virus.

Biopolis continued to expand. Many new facilities have been added to the park over the past ten years, including four major structures to house institutes for research in immunology, medical biology, molecular engineering, and neurology, commercial offices and laboratories, and retail businesses. Still on the drawing board are twin towers that will provide additional lab space to meet swelling demand.

Today, Biopolis is an important part of Singapore’s US$30 billion biomedical economy. During its eleven years in operation, it has created jobs, improved Singaporeans’ quality of life, and carved out a spot for the city-state on the world’s scientific map. More than fifty life science companies are involved in translational and clinical research in and around Biopolis, in collaboration with A*STAR institutes and life scientists and biomedical researchers at the National University.

“Biopolis was conceived as a key pillar of Singapore’s econ-omy,” says Lim Chuan Poh, A*STAR’s current chairman. “That conception has become a reality. Today, it is a thriving eco-system of public research institutions and corporate labs and a vibrant community of local and international biomedical scientists carrying out world-class research.”

The Biopolis research ecosystem fosters academic-government-industry collaborations


B ritain got off to a slow start in commer-cial biotechnology, especially considering the importance of British scientists and research institutions in the brilliant rise of molecular biology. But the country has

made a comeback.

One of the great technical pillars of the life sciences industry, hybridoma technology, was invented in 1975 at the British Medical Research Council’s famed Laboratory of Molecular Biology (LMB) in Cambridge. It was a method for producing monoclonal antibodies. The inventors, Swiss cell biologist Georges Köhler and Argentine biochemist César Milstein, reported the breakthrough in a 1975 paper in Nature. They concluded the article by stating that the technique “could be valuable for medical and industrial use.”

That turned out to be true. Today, monoclonal antibody products generate annual revenues in excess of $80 billion worldwide. Although he was personally ambivalent about privatizing academic research, Milstein approached the Medical Research Council (MRC) to recommend that a patent application be filed. After a cursory investigation, an MRC reviewer judged that the invention did not merit the filing expense. Americans rushed in to commercialize the technology.

A sympathetic stateside observer, Harvard immunologist Fred S. Rosen, wrote: “Anonymous administrators responsible for such decisions should be publicly exposed for their bad judgment and in-competence. Perhaps the time has come to restore the stockades and gallows at Tyburn as a way of reintro-ducing accountability.” The history of biotechnology might look very different today had it begun with the British in control of monoclonal antibodies.

In any event, Britain is back in the biotech race, and Cambridge is its swiftest runner. It’s a medieval town—William of Normandy built a castle there in 1068 and Cambridge University was founded in 1209—but in twenty-first century biology, it is state-of-the-art.

The university’s life science departments vie with Harvard, MIT, and Stanford for top rankings, and many other world-class academic institutions, including Addenbrooke’s Hospital, the Babraham Institute, the European Bioinformatics Institute, the LMB, and the Sanger Institute (formerly the Sanger

The “Cambridge Phenomenon” Cottages, Colleges, and Science ParksBiotechnology in England’s green and pleasant land

St. John’s Chapel, Cambridge University. The university was founded more than 800 years ago.



Centre), make Cambridge a vital center of basic biological research.

In the late 1960s, technology spillovers from university laboratories created the “Cambridge Phenomenon,” an efflo-rescence of entrepreneurship and innovation across the Fens. The Cambridge Science Park was built in 1970 to accommodate university spinoff companies and corporations engaged in university-industry research partnerships.

Initially, most of the action was in electronics and comput-ing—the area became known as “Silicon Fen”—but life science startups began to appear in the 1980s. Today, the park serves as an outpost for big biotech and big pharma companies, including Amgen, AstraZeneca, Bayer, Genzyme, and Sigma-Aldrich.

In addition, Granta Park, established in 1997 in nearby Great Abington, lists Gilead Sciences, MedImmune, and Pfizer Regenerative Medicine as tenants, and the Babraham Research Campus serves as an incubator for more than thirty small biomedical, biotechnological, pharmaceutical, and healthcare services companies. Biotechnology has become an important part of the “Cambridge Phenomenon.”

And fittingly, the town has acquired all the accoutrements of a thriving high tech cluster and innovation ecosystem. Leading British, European, and American venture capital firms have opened offices in Cambridge, and a strong base of angel investors has emerged to support local business development. Some have organized. The Cambridge Angels, for example, are a group of high net worth investors with experience as successful entrepre-neurs in internet, software, infotech, and biotech ventures.

The university offers a wide range of specialized educational

offerings in the life sciences and the business of biotechnology, and local nonprofit organizations such as the Cambridge Network and Biology in Business have generated training and networking programs for students, scientists, and biotech professionals.

One Nucleus, a Cambridge-based trade association with more than 500 member organizations, is working to integrate British companies into global life sciences, biotech, and health-care networks. The group was formed in 2010 by the merger of the London Biotechnology Network (LBN) and the Cam-bridge-based East of England Biotechnology Initiative (ERBI). CEO Harriet Fear has established relationships with sister organizations in the United States, Europe, Asia, and Australia.

So, the Cambridge cluster of biotech firms has become fully networked and globally connected. It has talent, infrastructure, and access to capital. Local leaders now want to avoid repeating past mistakes—they don’t want to let big fish technologies swim away down the River Cam.

Last year, Cambridge Innovation Capital (CIC), a partnership between Cambridge University, several London investment banks, and ARM, a Cambridge-headquartered semiconductor and software multinational corporation, was established for this express purpose.

The firm intends to distribute £50 million over three years to discovery stage life science startups built around Cambridge University technologies. According to CIC chairman Edward Benthall, the objective is to encourage Cambridge University spinoff companies “not to flip technologies to US corporations, but rather to build big businesses.”

The British Medical Research Council’s Laboratory of Molecular Biology opened a new facility in 2013. It was paid for, in part, by royalties from sales of the institution’s antibodies.


D uBiotech (the Dubai Biotechnology & Research Park) is part of an effort to attract foreign investment, diversify the oil-dependent

economy of the United Arab Emirates (UAE), and establish Dubai, the country’s most populous city and emirate, as a key node in global healthcare and high technology networks.

Dubai has been a hub of Persian Gulf commerce since the late nineteenth century. If the hopes of the emirate’s economic planners are realized, it will soon become a preferred location for foreign producers of goods and services targeting emerging markets in the Middle East, Asia, and Africa.

DuBiotech is the brainchild of His Highness Sheikh Mohammed Bin Rashid Al Maktoum, vice president and prime minister of the UAE and ruler of Dubai. “We have been working very hard to bring our country and society into the knowledge age,” he said at a launch event for the park in February 2005. “It is a historic transformation. It entails recon-sidering all our activities, regulations, and rules for work and education, as well as the structure of our government and economy.”

The Sheikh’s objective is to make Du-Biotech the largest center of life sciences research and development in the Middle East. Foreign companies have many incentives to become part of it. The park

is one of Dubai’s twenty-two free trade zones. The emirate allows 100 percent foreign ownership and full repatriation of profits and capital to firms that establish a presence in the zone. Firms are also exempt from customs duties on imported goods and services and from all corporate income taxes for fifty years.

DuBiotech offers attractive leasing options and a host of client services, including expedited registration and licensing of products for distribution and sale in the UAE, guidance on environ-mental, public health, and safety regula-tions, and matchmaking help to facilitate partnerships with local and regional companies and organizations.

The project came together quickly when the details of the incentive pack-age were announced and Germany’s Frankfurt Biotechnology Innovation Centre agreed to assist in infrastructure development. The park has been designed to accommodate a variety of businesses, from startups to multinational corpora-tions. Its office and laboratory spaces can be tailored to meet virtually any set of needs.

The key ingredients that Dubai and DuBiotech lack are a critical mass of scientific talent and an appropriately trained workforce. As Mohammed Yahia, editor of the Abu Dhabi periodical, Nature Middle East, points out, the nature of these shortcomings is such that it may take an extended period, many years,

DuBiotech: Watering a Desert FlowerDubai invests in infrastructure and offers incentives for foreign investment

“We have been working very hard to bring our country and society into the knowledge age.”Sheikh Mohammed Bin RashidAl Maktoum Vice president and prime minister of the UAE and ruler of Dubai



before the success of DuBiotech’s efforts to become a gateway to eastern markets can be assured. “To create such a hub and make sure it is sustainable,” he says, “you need to build up Dubai’s science community. You need to have a robust scientific culture in place, and that is not created overnight.”

Marwan Abdulaziz Janahi, DuBiotech’s director of business development acknowledges the challenge. “We are trying to bridge this gap,” he says. In 2006, the University of Sharjah, one of the UAE’s leading academic institutions, joined the project and pledged to foster university-industry collaborations. At the press conference announcing the agreement, which included plans to expand and improve academic programs for biotech workforce development, DuBiotech’s executive director, Abdul-qader Al Khayat, said, “Research done at universities has been one of the key drivers of the biotech industry and we are keen to develop this here.”

Regional science and education may or may not become a competitive advantage, but DuBiotech has continued to grow. In 2007, it broke ground for the construction of a state-of-the-art laboratory and office complex, and the municipal government, in partnership with Mubadala Development, a diversified investment company controlled by the government of Abu Dhabi, and LabCorp, an American clinical laboratory operator, established a branch of Dubai’s National Reference Laboratory in the park. Light manufacturing, packaging, and warehouse and shipping facilities were added in 2010.

More than 150 life sciences companies currently reside in DuBiotech, including leading American and European

biopharmaceutical corporations such as Amgen, Bayer, Bris-tol-Myers Squibb, Sanofi’s Genzyme, Merck Serono, and Pfizer. Many have set up regional headquarters in DuBiotech, and partnered with local contract manufacturers and regional distributors.

The park’s new headquarters are slated to open in 2015. Like all of DuBiotech’s buildings, the 500,000 square foot, twenty-two story structure will be green—LEED-certified for energy efficiency. Looking ahead, DuBiotech’s planners have drawn up blueprints for a self-contained biotech city with residential hous-ing, schools, a hospital, retail sales and entertainment centers, and a nature preserve.

The science park already has an impressive roster of com-panies in residence, and with 30 million square feet of space in which to grow, DuBiotech may succeed in turning Sheikh Al Maktoum’s dream into a reality.

An artist’s rendering of Dubiotech headquarters, currently under construction, slated to open in 2015below: Dubai, population 2.1 million


I f you’ve heard of Shenzhen – a city of fifteen million people in Guangdong province in southern China – you’ve prob-ably heard of its electronics industry. In 1979, Shenzhen became China’s first Special Economic Zone: a city designat-ed for entrepreneurial capitalism and trade with Europe and

North America.

With three hundred skyscrapers built in the 1980s alone, Shenzhen was transformed from a small fishing town on the Pearl River delta into a sprawling city. In 2014, Shenzhen’s boom continues apace. Its location helps. Only the Shenzhen River separates the city from Hong Kong’s prosperous New Territories. Cross-border traffic on rail, motor vehicle, and pedestrian bridges is heavy.

Shenzhen’s economic explosion has been powered by electronics manufacturing. Foxconn – the Taiwanese company that assembles Apple’s iPhones and iPads – owns Shenzhen’s best known factory complex, but many other electronics, computing, and telecommunications firms, Chinese and foreign, have op-erations in Shenzhen, including Dingoo, Hasee, Huawei, Netac, Skyworth, Coolpad, and ZTE.

The prospect of well-paid work has attracted young people from all over China. The streets of downtown Shenzhen have the feel of an oversized university campus—everyone seems under thirty.

Recently, Shenzhen has also begun to attract international attention for its biotechnologies. In 2007, BGI (formerly the Beijing Genomics Institute) relocated its headquarters from the capital to Shenzhen. The city government offered the company tax incentives and three years of free rent on a building in its Beishan Industrial Park.

BGI has expanded rapidly since then, under the leadership of cofounder and Chairman Henry Yang. It now employs 3,000 people in a wide variety of ambitious, large-scale initiatives, including the International Cancer Genome Project, the 1,000 Mendelian Disorders Project, the 1,000 Plants and Animals Genome Project, the 10,000 Microbial Genomes Project, as well

as efforts to sequence the genomes of the SARS virus, the giant panda, the silkworm, and plants, including rice, cucumber, and soybean.

BGI is also employing its high-throughput sequencing and bioinformatics tools to ramp up capabilities in transcriptomics, proteomics, and metabolomics. According to its leaders, the organization’s primary goals are to contribute to better under-standings of human health and to reduce the costs of health care, both in China and overseas.

Some observers are skeptical of the rhetoric, but the firm has begun to deliver. For example, BGI and Shenzhen health

BGI: “Experience a Brilliant Life”Startup culture in Shenzhen’s “biology factory”

Hong Kong’s next-door neighbor, Shenzhen, is known as China’s Silicon Valley. More than 300 skyscrapers were built in the city in the 1980s.



authorities have worked together to provide non-invasive prena-tal genetic tests to local residents at prices that ensure coverage under public health insurance schemes.

BGI’s employees are inspired and motivated by the mission. Several of the company’s arms (such as BGI Tech, BGI Health, and BGI Agriculture) are operated as for-profit companies, but the enterprise as a whole remains not-for-profit, and much of its work is funded by government grants. At present, profits generated by BGI’s commercial operations are reinvested to fund research and development.

The nature of BGI’s work invites comparisons with Shen-zhen’s electronics industry. BGI is often called a “biology factory,” which does for genome sequencing what Foxconn and others have done for consumer electronics. Many of its projects are notable for their size and their scaling trajectories—more and more people and machines are being deployed to sequence genomes at accelerating rates with increasing efficiency.

But the Shenzhen labs feel more like a start-up than a factory. There is little structured discipline. Staffers are free to come, go, and work as they please, working late into the night and sleeping through the mornings, or napping at their desks in the afternoon.

The hierarchy is minimal. Business attire is not required and rarely glimpsed. Individuals are judged on their demonstrated abilities to work in teams that generate high quality publications and innovative technologies.

Shenzhen has become China’s Silicon Valley, and BGI aspires to be its Google. Google’s mantra is “Do No Evil.” BGI urges employees to “Build a Magnificent Industry” and “Experience a Brilliant Life.”

The opening scene of a recent documentary film, Bregtje van der Haak’s DNA Dreams (2013), shows BGI Chairman Yang delivering a rousing “I have a dream” speech at the 2011 International Conference on Genomics. His is a techno- humanist dream of solving the world’s health problems through biomedicine.

BGI’s employees believe in Yang’s vision. They are highly educated, driven by a desire to have an impact on the world, and deeply devoted to their jobs. Their social lives revolve around the organization’s community-building efforts: social clubs, sports and fitness teams, extracurricular hobby and activity groups. Many have brought their families (including parents and sib-lings) to live with them in BGI housing. This all-encompassing environment breeds devotion to the organization’s goals.

At the moment, BGI seems enriched in possibilities. It is producing a quarter of the world’s genomics data, and the future may be wrapped inside its youthful and ambitious gene dreams.

Illumina Hiseq 2000 sequencers at BGI

Francis Collins (center), director of the US National Institutes of Health, with BGI employees during a 2010 visit to Shenzhen


C hilean biochemist Pablo Valenzuela is an original biotech pioneer. With scientific colleagues Bill Rutter and Ed Penhoet, he cofounded the Chiron Corporation in the San Francisco Bay Area in 1981. Rutter served as the company’s chairman. Penhoet

was appointed president and CEO. As vice president of research and development, Valenzu-

ela directed a remarkable series of scientific breakthroughs, including the invention of the first recombinant vaccine for hepatitis B, the first complete sequence of the HIV genome, and the discovery of the hepatitis C virus.

Throughout his tenure at Chiron, Valenzuela harbored a desire to spark scientific, biomedical, and industrial innovation in his homeland. In 1986, he established BiosChile in Santiago, a commercial manufacturer of scientific tools—reagents, labo-ratory equipment, instrumentation, and medical diagnostics. It was Chile’s first molecular biology company.

Five years later, BiosChile created a San Francisco Bay Area subsidiary called Austral Biologicals to manufacture a wide range of proteins used in biological and biomedical research—antibodies, antigens, growth factors, and transcription factors. In 2001, the company spun out its clinical diagnostics business to form a new company in partnership with Grupo CH Werfen SA, a Spanish firm. Together, the three units are called Grupo Bios.

In 1997, Valenzuela founded a nonprofit research institute in Santiago, the Fundación Ciencia y Vida (FCV), with his wife, Dr. Bernardita Méndez, who also served Chiron as vice president of regulatory and quality affairs. They formed the organization to conduct world-class biological research to spur the development of a national biotechnology industry, and to help Chile move into full participation in the global knowledge economy.

The FCV has assembled a wide range of programs to advance Chilean science, facilitate academic-industry

La Fundación Ciencia & Vida: Bioscience and Industry in the AndesA unique organization moves Chile into the global knowledge economy

Santiago, Chile; population 6.3 million



partnerships, foster scientific entrepreneurship, and enrich Chilean science education. Valenzuela, Méndez, and commit-ted colleagues in Santiago are true believers: they are confident that scientific progress will drive growth in the Chilean economy, and contribute to the vitality and welfare of Chilean society and culture.

FCV researchers conduct basic scientific investigations, but they also seek innovative solutions to practical problems confronting Chilean industries. The Chilean economy is based largely on natural resource extraction. Its largest industrial sectors are agriculture, aquaculture, mining, and forestry. The FCV has established research programs designed to shift the basis of growth in these areas from intensified resource exploitation to advances in knowledge and technology.

The goal is to reduce environmental degradation and introduce sustainable resource management systems while improving the quality and quantity of industrial outputs and enhancing Chile’s ability to compete in global markets.

The FCV’s industrial research projects have included efforts to engineer trees for improved cellulose and wood production, microbes for “bioleaching” in the industrial recovery of copper and other metals, and vaccines to fight bacterial and viral infec-tions that reduce yields in fruit cultivation and salmon farming.

The development of Chile’s human and intellectual capital is another important part of the organization’s mission. In many different ways, the Fundación works to create envi-ronments conducive to excellence in scientific discovery and technological innovation.

The FCV’s long-term strategy for strengthening Chile’s scientific culture entails investments in grassroots science ed-ucation. Several programs are underway. To achieve near-term results, the Fundación has established international exchange

and training programs for PhD students in the sciences at Chilean universities.

These programs include opportunities for learning not just about science, but about the business of biotechnology as well. At the FCV, students can take courses in entrepreneurship, management, finance, regulatory affairs, technology transfer policy and practice, and intellectual property law.

And in order to stimulate public and private investment in basic and applied science, technology development, and entrepreneurial ventures, the FCV is working to educate Chile’s political and business leaders about the importance of the life sciences for the nation’s economic future. The message has been received. In 2006, the Chilean government allocated funds to open a science and business park at the FCV to attract and support entrepreneurial biotech ventures, both foreign and domestic.

The park currently provides laboratory and office space for several companies headquartered in the United States, new Chilean companies affiliated with Start-Up Chile, a govern-ment program established to assist technology ventures, and spinoffs from the FCV, such as Andes Biotechnologies, which Valenzuela founded in 2008 with long-time colleagues, bio-chemists Luis Burzio and Arturo Yudelevich, to pursue novel anticancer therapeutics.

The FCV’s programs in education, basic science, applied science, and business creation are helping Chile build a scien-tific infrastructure and a self-sustaining innovation ecosystem that—despite being geographically remote—is integrated into the global knowledge economy.

When Pablo Valenzuela and Bernardita Méndez created the Fundación Ciencia y Vida, they envisioned a thriving Chilean biotech industry. It may be taking shape.

Pablo Valenzuela and Bernardita Méndez, founders of La Fundación Ciencia y Vida


Hamsters were instrumental in the development of molecular biology during the second half of the twentieth century, literally. Females imported from China donated ovary cells that enabled academic scientists to overcome technical obstacles and make early progress in the study of mammalian genetics. Later, the cells enabled industrial scientists to overcome technical obstacles and make early progress in the production of recombinant proteins. Today, Chinese hamster ovary (CHO) cells remain indispensable tools in both science and industry, and they may help translational scientists, pharmaceutical developers, and bioprocess engineers solve intractable problems in twenty-first century biomedicine and healthcare economics.


In the late fall of 1948, the Chinese civil war was approaching its climactic final scenes. As Mao Tse-Tung’s communist forces marched across the country’s northern provinces, a truck carrying a nondescript crate made its way from Peking to the republican capital of Nanking. The crate contained twenty compartments lined with wood shavings; each housed a Chinese hamster. There were ten males and ten females.

The hamsters were a gift from Dr. H.C. Hu of the Peking Union Medical College to Dr. Robert Briggs Watson, an American physician studying malaria in Asia for the Rocke-feller Foundation’s International Health Division. Watson was retrieving the animals for Victor Schwentker, a skilled rodent breeder in upstate New York. Schwentker had learned that the hamsters were valuable in biological and biomedical research. He also knew that it would be impossible to procure them after the Communists came to power.

On December 6, the hamsters were delivered to Watson’s doorstep. Nanking was being evacuated. Only the Yangtze River separated the city from the Maoists. Watson was preparing to flee, while suffering from dysentery and a respiratory infection. On December 10, he packed his laboratory equipment into a station wagon. He packed the hamsters as well.

Against the advice of Chinese friends and the American Embassy, he braved an eleven-hour drive through blinding rain, first to Wuxi and then on to Shanghai, narrowly avoiding mud-slides and roving bands of Communist troops, as the hamsters chattered away in their compartments.

The hamsters escaped China on December 12, 1948, on one of the last Pan-Am flights out of Shanghai. After the Maoists claimed victory and established the new People’s Republic, Wat-son was accused of “war crimes” by the Chinese Germ Warfare Commission and tried in absentia for conspiring with Chinese nationalists on behalf of the US government to carry out a biological attack. H.C. Hu was also charged. He was convicted and sent to a detention camp for six months of “reeducation.”

The hamsters landed in San Francisco, and were shipped to Schwentker’s farm in New York. More than six decades later, cell lines originating from Hu’s hamsters continue to serve as important tools in biomedical research and living factories for the manufacture of life-saving drugs.

A reluctant lab animalIn 1919, Dr. E.T. Hsieh of the Peking Union Medical College

became the first researcher to bring Chinese hamsters into the laboratory. He needed animals to inoculate, in order to distin-guish strains of disease-causing pneumococcal bacteria. Mice were scarce, but hamsters were abundant in the fields surround-ing Peking.

Five years later, Jocelyn Smyly, an Irish doctor working at the college, and American colleague Charles Young showed that Chinese hamsters were easily infected with the protozoan parasites that cause leishmaniasis (black fever). Soon, research-ers throughout China were using captured Chinese hamsters to study a range of infectious diseases including tuberculosis, influenza, diphtheria, and rabies.

Unfortunately, the rodents couldn’t be bred in captivity. Dr. Marshall Hertig made several attempts at Peking Union begin-ning in 1928, while he worked with Smyly and Young on leish-maniasis. When he left, he shipped 150 hamsters to the United States to establish a colony at the Harvard Medical School.

The attempt was an abysmal failure. The animals survived the bitter New England winter, but did not reproduce. Hertig built natural mating burrows in the basement of Harvard’s Compara-tive Pathology building, and later in the grassy yard outside, but to no avail.

Scientists did not give up trying to domesticate and breed Chinese hamsters. They recognized that the hamster was an exceptionally useful animal model for genetic research. They become sexually active at two months, and their gestation period is only three weeks. Several generations could be studied in a single year.

In 1943, Italian geneticist Guido Pontecorvo came up with another good reason for using them. He spread metaphase ham-ster cell nuclei on microscope slides and—with the low-resolu-tion instruments available to him at the University of Glasgow’s Department of Zoology—counted fourteen large chromosomes.

Robert Briggs Watson in the 1920s

Pan-Am routes in the Americas and across the Pacific in 1947


Watson’s DiaryDecember 1948, Nanking to Shanghai

Diabetic HamstersIn the late 1950s, George Yerganian noticed that repeat-ed inbreeding produced lines in which the hamsters uniformly developed symptoms of adult-onset diabetes, including periodontal, pancreatic, and retinal problems. For the next decade, he published papers on these and other pathologies with collaborators from Boston area hospitals and universities, and widely distributed diabet-ic hamsters to research laboratories and pharmaceutical companies in Europe and North America. Teams at the Upjohn Company of Kalamazoo, Michigan and the Charles H. Best Institute in Toronto bred the animals and established new colonies. Eventually, biomedical re-searchers around the world adopted the Chinese hamster as a standard animal model in which to study the appear-ance and progression of spontaneous diabetes. Yerga-nian’s Boston University vivarium was the point of origin.

A Chinese hamster


Mice have forty. Rats have forty-two. The size and low number of the hamster chromosomes facil-

itated cytogenetic research. Given the methods of the day, they were the easiest rodent chromosomes to identify, characterize, and map. Geneticists came to covet the animals, and persisted in breeding experiments.

Hamster whisperersVictor Schwentker decided to try his hand, too. He had

a thriving animal supply business in Brant Lake, New York, seventy miles north of Albany. He bred mice, rats, voles, moles, rabbits, hamsters and guinea pigs. By 1948, he had become the largest supplier of animals to biological laboratories in the northeastern United States.

Schwentker knew that demand for Chinese hamsters would be high. He found Robert Briggs Watson in China, through con-tacts among his biomedical research customers, and arranged to have some of the animals shipped to the United States.

Where others had failed, Schwentker managed to domesticate and breed the creatures in captivity. The process entailed a great deal of labor intensive taming. Within two years, Schwentker had a thriving colony, the first established outside of China. Word spread, and researchers started placing orders.

George Yerganian, a graduate student at Harvard, was one of them. He was conducting doctoral research on plant genetics, but in 1948, he found Pontecorvo’s paper in a Harvard Library, and realized that the hamsters’ low chromosome count would make the species a preferred experimental model. He purchased several animals in order to study their estrous cycles and mating habits.

In 1951, Yerganian began working on a postdoctoral fellow-ship in radiation biology at the Brookhaven National Laboratory on Long Island. He gained access to microscopes more powerful than those used by Pontecorvo and determined the correct number of chromosomes in Chinese hamsters: twenty-two. Two other cytogeneticists reached the same conclusion independent-ly, Robert Matthey at the Université de Lausanne in Switzerland, and Leo Sachs at the John Innes Institute in Norwich, England.

Schwentker discontinued sales of Chinese hamsters in 1954. They were popular with researchers, but the animals are natural-ly solitary, and females became aggressive in captivity. Raising and breeding them was difficult and laborious. Schwentker

never published or shared his breeding techniques, but by 1954, Yerganian had devised his own hamster-taming methods.

Yerganian had accepted a joint appointment the year before at Boston University and the Children’s Cancer Research Foundation (which later became the Dana-Farber Cancer Institute). With funds granted by the National Cancer Institute, he established a breeding center and began distributing hamsters to scientific colleagues. For the next decade, he was the sole supplier of Chinese hamsters to biomedical research institutions in the United States.

In 1983, Yerganian launched a private company, Cytogen Research and Development, Inc., to supply Chinese hamsters to public, non-profit, and commercial research laboratories. For many years, the company’s facilities were located on the Brandeis University campus in Waltham, Massachusetts.

“The mammalian E. Coli” In the 1950s, studies in human and animal genetics were

hindered by a lack of mammalian cell lines. Researchers had tried for decades to grow ex vivo animal cell cultures, but cells typically survived for just a few division cycles. Efforts to gen-erate and maintain continuously growing mammalian cell lines ended routinely in failure and frustration. Contamination by bacteria and molds was common, but even when this problem was solved in the 1940s by the introduction of antibiotics, the long-term viability of animal cell cultures did not improve.

There were exceptions. In 1943, Wilton Earle and colleagues propagated the first continuously growing mammalian cell line, mouse L, at the National Cancer Institute, and in 1951, Dr. George Gey grew the first immortal human cells, the famous HeLa line, at the Johns Hopkins University School of Medicine. But these cultures were mixtures of heterogeneous cells, many of which contained chromosomal abnormalities. For many inquiries, Mouse L and HeLa cells had limited utility.

Important advances were made in 1948 when


Earle’s lab established a clonal (genetically homogenous) mouse L culture, called mouse L929, and in 1955, when geneticist Theodore Puck managed to isolate and propagate single clones and establish clonal HeLa cultures at the University of Colorado School of Medicine in Denver.

Researchers in Puck’s laboratory went on to develop novel in vitro culturing techniques, special growth media for mammalian cells, a large collection of useful human and animal cell lines, and methods for mutagenesis and gene mapping that enabled—for the first time—studies of molecular genetics in mammalian cells.

In 1957, Puck learned of the Chinese hamster and its compact genome. He contacted George Yerganian and asked for specimens. Yerganian sent a single adult female, housed in a handmade box with a mesh top. She arrived by railway courier, after riding trains for several days. No one could have predicted how important this single hamster would become in the history of the life sciences, biomedicine, and the biopharmaceutical industry.

Puck removed an ovary, extracted a cell, and gently coaxed it into expansion in a petri dish. It was the first culture derived from a Chinese hamster. Puck found that with proper treatment, CHO cell cultures grew quickly. The cells were hardy and could be maintained indefinitely. By subcloning, Puck and a junior colleague, Fa-Ten Kao, generated the CHO-K1 cell line, which became a standard research tool in molecular and cell biology.

Labs from around the world requested cells from Denver, and Puck distributed them freely. His CHO cell lines became the gold standard for in vitro studies of mammalian biology. He took to calling them “the mammalian E. coli.” Molecular genetics had previously advanced mainly through studies of microbes—virus-es, bacteria, and fungi. After 1957, thanks largely to Puck and the unique properties of CHO cells, geneticists had new opportuni-ties to study higher organisms.

Add sugarIn 1973 and 1974, University of California, San Francisco

biochemist Herbert Boyer and Stanford University geneticist Stanley Cohen conducted a series of experiments that demon-strated the utility and power of recombinant DNA technology as

an instrument of genetic engineering. The invention set the stage for the birth of the biotechnology industry.

Genentech, the first company established to commercialize the technology, made headlines in 1978 and 1979 when it reported the manufacture of medically useful peptide hormones, first insulin and then human growth hormone, in bacteria, in E. coli—naturally, because molecular biologists knew far more about E. coli cells than other any kind. They had been studying E. coli for decades. Researchers had developed an intuitive feel for its behaviors, proclivities, moods, and reactions.

Genentech’s accomplishments were impressive, and they stirred competition. Many molecular biologists were encour-aged to reproduce the company’s success with other genes and molecules of commercial value. A host of biotech startups sprang up, endowed with sufficient capital to explore the potentially lucrative new field.

After insulin and growth hormone, Genentech selected the gene for tissue plasminogen activator (tPA) as a cloning priority. So did several competitors. tPA is a blood clot dissolving protein. It was considered a promising treatment for heart attacks. The size of the potential market made it an enticing target.

Genentech scientists isolated the gene and plugged it into the E. coli expression system that had produced insulin and human growth hormone. This time, the result was different. Dennis Kleid, one of the company’s early cloners, reports that the bacteria made only half-hearted efforts to express the molecule. “Just tiny amounts were detected,” he says, “and the protein wasn’t folded properly.”

The failure was a reality check. Researchers at Genentech and competing firms had hoped that simple prokaryotic cells would be suitable for the commercial production of a wide range of large, complex human proteins. The tPA experience gave them pause.

The post-mortem drew attention to the many post-trans-lational modifications that cells make to turn amino acid chains into functional proteins. In human beings, the process is complex; prokaryotic bacterial cells don’t possess the same modification repertoires. In the tPA experiment, the molecule hadn’t folded properly because E. coli isn’t fully equipped for mammalian glycosylation.

Glycosylation is an enzymatic process in which sugar groups are linked covalently to newly synthesized proteins. The sugars cause the proteins to fold into stable, soluble forms. Early exper-iments with E. coli and other microbes taught gene cloners that prokaryotic cells would not turn some heterologous (foreign) gene products into biologically active molecules. tPA was one of them.

The use of E. coli as a recombinant protein factory gave rise to other sorts of problems. In 1980, for example, Genentech came to a dead end in its quest to make a recombinant hepatitis B vaccine. When company scientists inserted the gene for a viral antigen into E. coli, the bacterium’s cellular machinery lurched to a halt. Dennis Kleid remembers the mishap: “E. coli hated that protein. The bacteria stopped growing. They just quit.”

Dr. Theodore Puck

The “Axel Patents”On February 25, 1980, Columbia University inventors, molecular biologist Richard Axel, microbiologist Saul J. Silverstein, and geneticist Michael H. Wigler, filed an application with the United States Patent and Trademark Office (USPTO) for a patent on the “Wigler method” of “co-transformation,” techniques for cloning and express-ing heterologous genes in nucleated eukaryotic cells. The Cohen and Boyer invention had described the re-engi-neering of non-nucleated prokaryotes, such as bacteria. The Wigler method became a standard tool in mamma-lian biology and genetics, biomedical research, and com-mercial biotech manufacturing. The USPTO issued the initial patent to Columbia University in 1983. The claims were broad. They covered many different vectors and cell types in the production of many different recombinant proteins, and the university made nine additional filings to extend, refine, and manage the patent estate. Ten firms, including Amgen, Biogen, Genentech, and Genetics In-stitute, purchased licenses at low “early bird” prices. After June 1, 1984, the university granted twenty-four addi-tional licenses at a higher rate. By the time the patents expired in August 2000, they had generated more than $790 million in royalties.


The problem stemmed from the fact that E. coli does not secrete proteins in large quantities. E. coli is a gram-negative bacterium. Its envelope has two membranes, each with different properties and functions. Genentech found that recombinant proteins generally don’t cross both of these barriers without assistance.

Consequently, recovery of proteins from E. coli entailed lysing the cells, which complicated the purification process and added to production costs. And in the case of the hepatitis B project, the presence of hepatitis antigen in the cytoplasm evidently caused enough discomfort that the cells stopped dividing.

The problems with E. coli prompted Genentech to hire Arthur Levinson, a postdoc at the University of California, San Francisco, to investigate eukaryotic expression systems. Levinson worked first to express the hepatitis antigen in yeast, and then he turned to mammalian cells. By August 1981, he had developed an experimental expression system in monkey kidney fibroblasts.

Amping upMammalian cell expression was a wide-open field, but

Levinson wasn’t the first entrant. By the time he began exper-imenting with monkey kidney cells, Michael Wigler, Richard Axel, Saul Silverstein, and colleagues at Columbia University had already been putting recombinant DNA into mouse cells for nearly three years. In 1979, they showed how to clone and express genes coding for desired proteins along with selectable markers. They filed a patent on the invention in February 1980.

But protein yields in early mammalian cell expression systems were disappointing. Research conducted several years before in the laboratory of Stanford biologist Robert Schimke provided means of improvement. In 1976, as Schimke was studying how cancer cells develop resistance to chemothera-peutic agents, one of his graduate students, Fred Alt, discovered a phenomenon called gene amplification.

Alt observed that when mouse sarcoma cells were exposed to methotrexate, a highly toxic cancer drug, most died but some became resistant and survived. He and Schimke investigated and found that methotrexate inhibits a vital enzyme called dihydrofolate reductase (DHFR). Somehow, resistant cells made tens or even hundreds of copies of the DHFR gene, which produced enough excess DHFR to overcome the methotrexate in the medium.

In their patent application and related papers, Axel and col-leagues at Columbia proposed that DHFR amplification could significantly increase gene expression in mammalian cells. A test of the idea became feasible in 1980, when Columbia cell biologists Lawrence Chasin and Gail Urlaub isolated mutant CHO cells that lacked the enzyme.

In 1982, a postdoc working in Phil Sharp’s MIT laboratory had the idea of engineering these DHFR-deficient cells for the production of recombinant proteins. Randy Kaufman had been a graduate student in Schimke’s lab at Stanford. He spliced the


DHFR gene into an engineered plasmid (a circular ring of DNA) adjacent to a gene that codes for a monkey virus (SV40) protein, and then introduced the plasmid into the DHFR-deficient CHO cell mutants.

He anticipated being able to select for cells that both survived exposure to methotrexate and produced the SV40 protein in large quantities—if, as he hoped, the cells generated copies of both linked genes. It worked. In fact, the genes from the plasmid were incorporated and amplified as part of the hamster genome. It was possible to increase yields.

On March 23, 1982, Kaufman and Sharp submitted an article on the work to the Journal of Molecular Biology. Kaufman sub-sequently constructed a vector for amplified expression of alpha interferon in CHO cells. He recalls encouraging Sharp to file for a patent on the invention, but the lab chief declined.

As a co-founder of Biogen—which was at the time working to develop alpha interferon as a pharmaceutical product—Sharp recognized the value of amplified gene expression in cells that could fold human proteins into proper shape, but he was satisfied that the Axel patent had wrapped up the territory. As it happened, Biogen didn’t use Kaufman’s system. The company’s manufacturing and marketing partner, Schering-Plough, made interferon in E. coli.

By the beginning of 1983, Genentech’s Levinson had also devised a DHFR expression system with help from Chris Simon-sen, another alumnus of Schimke’s lab. The pair filed a patent application on January 19. Later in the year, Kaufman took his CHO cell expertise to Genetics Institute in Boston, where he worked on the production of tPA, erythropoietin (EPO), a red blood cell growth-stimulating hormone, and Factor VIII, a blood clotting factor.

Scaling upSuccess in boosting CHO cell expression created a new set

of problems. Once companies learned how to make proteins in CHO cells, they had to install manufacturing processes. Mam-malian cell cultures had never been grown on industrial scales. In the early 1980s, it was generally assumed that they were not well suited to growth in suspension in fermentation tanks. CHO cell manufacturing became a technological adventure.

Growth media in high volume bioreactors are stirred in order to maintain optimal or at least workable environmental con-ditions—temperatures, pH levels, oxygen transfer rates, broth consistencies, and cell densities, for example. Precision control is necessary to achieve efficiency and quality in production, but stirring creates turbulence in growth media and shear forces greater than fragile mammalian cells can withstand.

In the early 1980s, all good cell biologists knew that mam-malian cell cultures grew best in roller bottles. Roller bottles are small vessels that contain liquid cell growth media. Cell cultures coat the interior surfaces in a thin monolayer, and the bottles are slowly rotated. The action alternately washes the cells in the growth medium and exposes them to air.

Genentech and other early biotech companies used roller bottles to grow mammalian cells that expressed and secreted functional recombinant human proteins, but when it came time to scale up, they had no blueprints to follow. No one had ever assembled an industrial scale mammalian cell culture produc-tion system. Company scientists had no idea how adaptable or scalable their processes would be, if at all. Everything was experimental.

Genentech ventured first into this uncharted territory as it prepared to introduce CHO cell-derived tPA. The initial task was to produce enough of the drug to supply clinical trials. Bill

Blockbuster drugs made in CHO cells

ProductSales (USD B)

Year of first Approval

Patent Expiry (US) Company

Humira (anti-TNF) 11.00 2002 2016 AbbVie; Eisai

Enbrel (anti-TNF) 8.76 1998 2028 Amgen; Pfizer; Takeda

Rituxan/MabThera (anti CD20) 7.91 1997 2016 Biogen Idec; Roche

Avastin (anti-VEGF) 6.97 2004 2017 Roche/Genentech

Herceptin (anti-HER2) 6.91 1998 2019 Roche/Genentech

Epogen (epoetin alfa) 3.35 1989 2013 Amgen; Johnson & Johnson

Avonex (IFN-ß-1a) 3.00 1996 2015 Biogen Idec

Rebif (IFN-ß-1a) 2.59 1998 2013 Merck Serono

Aranesp/Nesp (darbepoetin α) 2.42 2001 2024 Amgen

Advate/Recombinate (Octocog α) 2.37 1992 Baxter

Eylea (anti-VEGF) 1.88 2011 2021 Regeneron; Bayer Healthcare

Total Sales in 2013 57.16


Young was Genentech’s head of manufacturing. He remembers that it was difficult to project demand—no one knew how much of the drug to administer to patients.

The trials began with very low doses, but the clinicians kept bucking them up. Young worked with calculations that started at 5 milligrams per dose and rose to 150 milligrams. Soon, he says, “It was almost impossible to make enough product in roller bottles. I could envision these bottles taking off over the entire building. It was the Rube Goldberg approach to biotech manufacturing. We just kept adding more and more bottles.” Genentech had a problem.

Young credits Jim Swartz with casually ushering in a new era of bioprocess engineering. Swartz was a chemical engineer who had come into the company from Eli Lilly and Company. According to Young, he asked, as the manu-facturing group mulled over its predicament, “’Why don’t we try growing these cells in a fermenter? We’ve got a 10,000-liter fermenter that we bought for bacterial work. How do we know that the cells won’t grow in it?’”

The cell biologists on staff repeated the conventional wisdom that mammalian cells are too delicate, but Dennis Kleid remem-bers a timely and influential suggestion from a contrarian, Rob Arathoon: “He suggested that we change the gear ratio on the impeller and stir the tank very, very slowly.” Some calculations indicated that gentle agitation could work for CHO cells, which grow relatively slowly and need less oxygen than E. coli. The idea gained traction.

Levinson worked with the company’s manufacturing group to design a bioprocessing system that would facilitate the growth of genetically engineered CHO cells in suspension in the 10,000-li-ter bioreactor. Young hired three industrial microbiologists from Burroughs Wellcome with experience in large-scale cultures for animal vaccines, and the project team worked through a host of technical and regulatory issues—purification, validation, risks of viral contamination, and so on—to deliver clinical grade tPA.

Young calls the scale up process “horrendous,” but somehow it all came together. In fact, the company discovered that CHO cells in suspension made a more potent product. When the big bioreactor went online, the medical staff had to back down rec-ommended doses from 150 to 100 milligrams. It was a mystery. “The molecule was different chemically,” says Young, “but we never found out exactly why.”

On November 13, 1987, Genentech’s tPA became the first FDA-approved pharmaceutical product manufactured in CHO cells. The commercial performance of the product was under-whelming, but the design and construction of the manufacturing system was genuinely innovative. “Nobody had ever done anything like this,” says Young. “It was a completely new way of making a pharmaceutical product.”

In the mid-to-late 1980s, many companies followed Ge-nentech’s lead and turned to eukaryotic cells as E. coli systems proved inadequate or inferior to viable alternatives. CHO cells

became, and they remain, preferred hosts for the production of recombinant protein therapeutics. Of the twenty top-selling biopharmaceuticals on the market in 2013, eleven were manu-factured in CHO cells. Combined annual sales of these protein products exceeded $57 billion.

Bioprocess optimizationOn May 2, 2014, Biogen CEO George Scangos delivered the

annual Michaels Lecture to the MIT Department of Chemical Engineering. He spoke about challenges and opportunities in bioprocessing and observed that since the 1980s, yields and costs in protein drug manufacturing have followed a biological analogue of Moore’s Law.

In 1965, Intel co-founder Gordon Moore predicted that transistor counts in integrated circuits and computing capacities and speeds would double every two years, and so they have. This year, Scangos explained to his MIT audience that outputs in biotech manufacturing have also increased exponentially. Cell biologists and bioprocess engineers have boosted cell culture yields from 100 milligrams per liter in the early 1980s (at a cost of $10,000 per gram) to 5 grams per liter today (at $100 per gram).

Advances in computing are now approaching physical barriers. Soon, it will be impossible to go smaller. According to Scangos, advances in bioprocess manufacturing are also pushing up against limits—not physical, but economic. Biogen currently controls 10 percent of the world’s mammalian cell culture capac-ity (Roche, Amgen, and Biogen together account for 55 percent of the total). Scangos believes that it has become infeasible for biotech manufacturing operations to continue leveraging classical economies of scale.

There are some further parallels. Physicists and electrical engineers contend that after the end of Moore’s Law, advances in computing power will result from greater energy efficiency and the emulation of materials and architectures in biological information processing systems—DNA, cells, and brains, for

Recombinant DNA Expression Systems

35.5% CHO cells

29% E. coli16.5% Misc. mammalian

16.5% Yeast

8.5% Misc.

4% Human

Biopharmaceutical applications (1982 to 2014)

Sequencing the CHO GenomeWhen plans for the CHO cell genome project were an-

nounced, many researchers hoped that it would lead to deeper understandings of CHO biology. They envisioned the creation of “designer” cells lines and vaulting advances in biopharmaceutical development. This promise has not yet been fully realized, but the field is moving rapidly from the manipulation of single genes to multiple gene orchestration.

In 2006, leading biotech and pharmaceutical companies joined forces with the Society for Biological Engineers to establish the CHO Consortium. Member organizations worked cooperatively to map and sequence the genomes of several different CHO cell lines, and agreed to share resulting

intellectual properties. Members had full access to the con-sortium’s extensive database. Participating companies includ-ed Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, SAFC Biosciences, and Schering Plough.

GT Life Sciences, a privately held San Diego firm, launched a second effort to sequence CHO cell line genomes, in partnership with the Beijing Genomics Institute (now BGI). In August 2011, the partners published the first open access CHO genome sequence, for the CHO-K1 cell line. Two months later, GT Life Sciences was acquired by Intrexon Corporation, a synthetic biology company located in the San Francisco Bay Area.


example. Similarly, Scangos maintains that future advances in bioprocessing will be realized through improved utilization of existing assets and the installation of flexible, networked communication, supply, and production processes.

On the technical side, cell biologists and bioprocess engineers continue to improve the utilization of the industry’s vital tools. They are learning how to make better bioreactors and growth media, and how to make cells healthier, happier, and more sociable—i.e., tolerant of increasing cell densities—in order to improve protein yields. Drug companies have developed a wide variety of CHO cell lines with genotypes, phenotypes, and behaviors adapted for expression of different kinds of recombi-nant proteins.

Hamster cell genomesIn the age of genomics and bioinformatics, these convention-

al efforts are swimming in great pools of new data. Researchers have gained access to the astoundingly complex universe of molecules and pathways that constitute mammalian cell drug factories. Nate Lewis, a systems biologist and assistant professor at UC San Diego School of Medicine who studies CHO cells, says, “In the past, researchers tweaked environmental condi-tions, or the vector with the inserted gene, but they never really knew what was going on inside the CHO cell itself. The cell was a black box.”

To open the black box, several big biotech and pharmaceu-tical companies launched a private consortium to sequence the genome of several CHO cell lines in 2006. In a former life as an industrial scientist, Lewis became part of a second sequencing ef-fort initiated by GT Life Sciences, because, he says, “The lack of a genome had really stalled CHO research. After the E. coli genome was sequenced, researchers were able to do metabolic engineering in bacteria. We wanted to be able to do it in CHO cells.”

Scientists are now using CHO genome sequences to provide detailed portraits of transcription, translation, protein synthesis, and post-translational modification in altered hamster cells. They are uncovering biomarkers that distinguish high-yield lines, and others that point to rate-limiting cellular processes.

They have shed light on hamster glycosylation pathways.

Vanishingly small variances in glycosylation can have dramatic impacts on drug efficacy, stability, and safety. The biochemical toolkit utilized by CHO cells resembles that found in human cells, but hamsters lack a few key enzymes, and they possess others that add non-human sugar modifications, which may diminish therapeutic efficacy or induce immune responses. All of this is grist for the molecular pharmacologist’s mill.

Drug makers are now combining their expanded knowledge base with precision tools for knocking genes down and out. In 2009, Alnylam of Cambridge, Massachusetts began applying RNA interference (RNAi) technology to silence select CHO cell genes. In May 2014, researchers at the Technical University of Denmark made the first demonstration of CHO genome editing with CRISPR/Cas9 technology. The targets included genes that diminish the efficacy of therapeutic antibodies.

Others researchers are attempting to create humanized CHO cell lines by knocking out CHO genes that code for enzymes involved in non-human modifications. Such an approach could enable CHO cells to mimic human glycosylation, and drug makers to produce safer, more efficacious medicines.

At UCSD, Lewis is taking a global “systems biology” view of CHO cell protein factories. He is using computational methods to build models of metabolic pathways involved in recombinant protein secretion. He has two goals. He wants first to generate predictive rules that researchers can use to determine optimal cell lines, media, and growth conditions for the high volume manufacture of specific proteins.

Secondly, he wants to develop predictive algorithms for engineering cell lines, biological systems that will produce high quality biotherapeutics displaying a wide range of desired characteristics, properties, and specificities. “With the genome sequence and these models in hand,” he says, “we will be able to control in a very specific manner the attributes of proteins.”

CHO cells, drug prices, and biosimilars

The metabolic engineering of mammalian cells can enhance the safety and efficacy of new biological drugs. It may also further improve biomanufacturing processes, reduce production


costs, and perhaps help to lower drug prices—at a time when healthcare expenditures are spiraling upwards and payers are exerting intensified pressure on drug companies to engage in deep discounting.

The biotech sector is at the center of the imbroglio because it has focused largely on the development of innovative specialty drugs and treatments for unmet medical needs. Branded biophar-maceuticals are often the best and sometimes the only treatment options available to doctors and patients, and in the age of genom-ics and precision medicine, these high value products frequently serve small patient populations. The prices are very high.

The economic pain has led payers—patients, providers, insurance carriers, pharmacy benefits managers, governments, taxpayers, employers, and labor unions—to question the value of the products. Are the benefits worth the great expense? When the question was put to Severin Schwan, CEO of the Swiss pharmaceu-tical company, F. Hoffman-LaRoche, he said, “There is no objective answer. At the end, you are discussing, what is the price of life?”

Schwan implies that the issue is for society to decide, not CEOs, accountants, or scientists. How much should we pay to take care of people? How much can we afford to pay? Who should decide, and on what basis? Schwan also implies that the prices are fair: the drugs give “life” and society at large must decide whether to pay for it.

Finally, he assumes relations of trust between corporations and communities, but these seem to have broken down. In public debates on pricing, drug companies are portrayed, in turn, as ethical firms doing their best to balance obligations to customers and shareholders, and as price gougers motivated by unbridled greed.

Industrialists maintain that the high prices reflect the realities of drug development: it is immensely difficult, enormously expensive, intensely competitive, and highly regulated. The vast majority of projects miscarry. Revenues from successful products must subsidize a host of failures. Innovation is a risky, costly business.

In November 2014, The Tufts University Center for the Study of Drug Development (CSDD) released an estimate of total de-velopment costs for a new FDA-approved pharmaceutical prod-uct in the United States: $2.6 billion. Critics are loath to accept the figure. Rohit Malpani, policy director of Doctors Without Borders told The Economist, “If you believe that, you probably also believe the earth is flat.” Skeptics complain that Tufts relied on information supplied by pharmaceutical companies.

The debate is heating up, but process improvements are unlikely to have substantial impacts on prices for patented biopharmaceuticals, because manufacturing costs represent only a small fraction of total expenditures. But even slight savings could make a difference in markets for generic products, where producers compete on the basis of price.

In the United States, biopharmaceutical manufacturers have not yet faced competition from off-brand products, but many first generation protein drugs will soon lose patent protection. A host of companies are gearing up to develop facsimiles.

The products are called “biosimilars” or “biological

follow-ons” rather than generics because they resemble the original products, but are not identical. The complexity of bio-logical molecules precludes the design of exact replicas. Protein products can vary from factory to factory even if the same host cells and manufacturing process are used.

Market penetration of biosimilars could be rapid in the United States if the products offer significant savings. A report published last year by the RAND Corporation estimated price cuts between 10 and 35 percent. Competition among small molecule generics typically cuts prices in half, but the biologicals will have higher production costs. They may also be required to clear significant regulatory hurdles.

The regulatory environment is unsettled. The 2010 Patient Protection and Affordable Care Act created an abbreviated licensing pathway for biological products that are “interchange-able” with licensed drugs, but the FDA is still finalizing regula-tions. If the rules favor developers, healthcare payers will surely gravitate to the cheaper alternatives.

Elsewhere around the world, the picture is clearer. The European Union established an approval process in 2004, and the first wave of products appeared two years later. As of May 2014, twenty products had been approved for sale. Investment in biosimilars production is also growing rapidly in China and In-dia, where high-cost branded biologics strain national healthcare systems. Demand is high for alternatives, and regulatory barriers are relatively low.

CHO cells have served as vital tools in the development of innovative protein therapeutics for more than thirty years. Now, they are helping drug makers deliver follow-ons at affordable prices to doctors and patients in more than fifty countries. If mo-lecular biologists can engineer CHO cells for more efficient cell culture production, the result will be better medicines at lower costs for millions of people around the world. n

Cell-Free Gene Expression and

Protein SynthesisGenetically engineered CHO cells may represent the future of biopharmaceutical production. Or they may have no future at all. Sutro Biopharma would prefer the latter outcome. The company is developing a cell-free gene expression platform as an alternative to in vivo cell culture and transgenic modes of production. The idea is to transcend limitations imposed by adapted bio-logical systems. Sutro’s alternative separates all cellular components required for transcription, translation, and protein synthesis into an extract. Users simply add DNA encoding desired proteins. The company claims that its technology optimizes biochemical processing and affords grams per liter yields in just eight to ten hours even at commercial production scales.


D iagnostics for All (DFA) is a nonprofit or-ganization located in Cambridge, Massa-chusetts with one mission: to revolution-ize public health on a global scale. Sixty percent of people in the developing world

lack access to adequate medical care. DFA is working to change that. The organization is developing inexpensive point-of-care diagnostic devices that can quickly read a patient’s health status without the use of power or water and without professional medical personnel.

DFA’s diagnostic tests employ a technology invented in the lab of Harvard University chemist George Wh-itesides in 2007. Reagents are printed in liquid-wicking grooves on paper to make a tiny microfluidic device, a “lab-on-a-postage stamp.” A single drop of blood from a finger-prick changes the color of the device to indicate the test result. The tests are fast, easy to use, and

biological waste disposal is simple. The paper can be incinerated after use.

Whitesides and cofounder Carmichael Roberts, a Massachusetts venture capitalist and former biotech executive, established Diagnostics for All in 2008. The startup attracted a group of young scientists and social entrepreneurs committed to improving access to healthcare in developing countries. Harvard University granted DFA an exclusive royalty-free license to the technology for not-for-profit applications.

DFA offers sublicenses to private ventures interested in commercializing the technology in resource-rich countries, but the organization relies primarily on char-itable donations, grants, and pro-bono contributions to support its operations and research.

The Bill and Melinda Gates Foundation has been a consistent backer. In May 2011, the Foundation awarded

Diagnostics for AllMiniature diagnostics, global impact

DFA’s diagnostic tests are embedded in paper panels about the size of a quarter. Fluid samples are placed on dots. Results are indicated by changing colors.

Global Biotech Philanthropy


a two-year grant of $2.9 million for the development of animal health diagnostics that will enable small-holder farmers in Sub-Saharan Africa to improve livestock care.

In December 2012, DFA received an additional $2.6 million to develop rapid tests that identify immune markers of successful vaccination against tetanus and measles, and in May 2014, another $1.2 million for a bovine estrus diagnostic that indicates when cows are ready for artificial insemination.

The organization’s medical tests diagnose a range of treatable conditions including tuberculosis, malaria, HIV, diabetes, and liver failure, a common side effect of drugs prescribed for tuberculosis and HIV/AIDS. In resource-rich areas, expensive medical equipment is used to monitor patients for early signs of liver complications. In developing countries, such monitoring costs are prohibitive. DFA’s finger-prick test to assess liver health in fifteen minutes is current-ly in field trials.

Innovations in the pipeline include quantitative devices developed jointly with University of Illinois chemist John Rogers and MC10, a Boston area consumer electronics company. They incorporate flexible electronic sensors, transistors, and batteries to provide digital readouts of biomarker levels. Pro-totypes detect micronutrient and vitamin deficiencies in children.

Conventional microfluidic diagnostic devices are designed for use with external readers in clinical laboratories—equipment that is unsuitable for field use in developing countries because it is expensive, fragile, and easily broken or stolen. DFA’s quantitative technologies do not require additional instrumentation.

The electronics work with the image processing

capabilities of mobile phones, which are now preva-lent in even the world’s most remote regions. Current DFA president and CEO Marcus Lovell Smith announced a successful trial in December 2013: “We were able to demonstrate a simple and reliable method for analyzing results and transmitting them by mobile phone.”

Many of DFA’s products are in final trials. Field use of the tests requires only minimal training and sample preparation. At a cost of just pennies per unit, paper diagnostics are poised to become foundational technologies for sustainable regional healthcare net-works that will reach the world’s most underserved and disadvantaged populations.

Harvard University chemist George Whitesides, co-founder of Diagnostics for All


I n a March 2004 press release, the US Food and Drug Administration announced that it had approved sales of Erbitux, a new biopharmaceutical from ImClone

Systems, Inc., of New York, New York, for the treatment of advanced colorectal cancer.

Three years earlier, the agency’s refusal to consider the company’s application for review of the product precip-itated an insider trading scandal that landed CEO Sam Waksal, Merrill Lynch broker Peter Bacanovic, and media personality Martha Stewart in prison. The episode was a public relations fiasco for the biotech industry, but there are other stories to tell about Erbitux and the people involved in its development.

Erbitux was invented by cell biologist Gordon Sato, in collaboration with two colleagues at the University of California, San Diego (UCSD): his son, Denry, who was working in his lab as postdoc, and John Mendelsohn, the founding director of the UCSD Cancer Center.

Erbitux and the

Manzanar Project

Drug royalties for coastal desert aquaculture

The Manzanar detention camp in California’s Owens Valley. More than 100,000 Japanese-Americans were held there during World War II.

Global Biotech Philanthropy


Sato trained for a PhD in biophysics at Caltech under Max Delbrück, and did postdoctoral work at the University of California, Berkeley with Gunther Stent, and the University of Colorado, Denver with Theodore Puck. He enjoyed a long, successful career, and was elected to the National Academy of Sciences in 1984, the same year Erbitux was invented.

Erbitux is the trade name for a chimeric (part murine, part human) anti-EGFR monoclonal antibody known generically as cetuximab. EFGR stands for epidermal growth factor receptor. It is overexpressed in a variety of solid tumors, including squa-mous cell cancers, carcinomas, melanomas, glioblastomas, and meningiomas.

Levels of EFGR overexpression correlate with rates of growth and metastasis, and prognoses for patients. Erbitux works by binding and blocking growth factor receptor sites on cancer cell surfaces. This prevents the downstream molecular signaling that initiates uncontrolled tumor cell division.

Sato retired from science in 1992 to work full-time on a humanitarian cause he had taken up a few years before—the de-velopment of sustainable aquaculture systems in coastal deserts subject to famine. He went to the drought-stricken East African country of Eritrea to construct fish farms and plant salt-tolerant mangrove trees in tidal areas on the Red Sea, to supply food for livestock and people.

The idea came from Sato’s experience as a teenager. He was born in Los Angeles and raised on Terminal Island, a Japanese community near the port of Long Beach. On February 9, 1942, the FBI incarcerated all of Terminal Island’s adult male Japanese immigrants, including Sato’s father. The families were given forty-eight hours to evacuate their homes, which were razed, and then sent to an internment camp in Manzanar, California, in the Owens Valley, the desert area beneath the eastern face of the Sierra Nevada.

Sato was fifteen at the time. It was at the camp that he first began thinking about self-sufficient desert communities: “Since I was a child,” he told a reporter in 2008, “I loved science and I envi-sioned science would help poor people, and it can. In Manzanar, I thought about the desert, and when I was in Africa I thought about the desert. It came from my experiences at Manzanar.” He named his coastal desert aquaculture program the Manzanar Project.

As Erbitux neared approval in 2004, Sato was in Eritrea. The New York Times reported that, as a co-inventor of the drug, he stood to receive several hundred thousand dollars a year in royal-ties from sales. When informed that he might be receiving some checks, Sato said, “I hope so, because I’m running out of money here.” By that time, Sato had reportedly spent half a million dollars on his personal African crusade.

Gordon Sato, fifteen years old, at Manzanar in 1943Sato (right) with research assistant Abraham Fesahe and newly planted Mangroves along Eritrea’s desert coast


The Art of Robert Schimke

photo finish

Stanford physician and cell biologist Robert T. Schimke took up art in 1976, at the age of forty-four. He turned to the pursuit at difficult times in his life, and experimented with various media and subject matters. His scientific career was ended and his artistic vocation in-terrupted when he suffered devastating injuries in a 1995 bicycling accident on a mountain road in Woodside, California. He experi-enced nearly complete paralysis, but by 2002 he had regained suffi-cient movement to return to painting. He subsequently worked with acrylics, temperas, and oils, and layered brush and drip techniques, to create vivid landscapes, floral designs, and abstract patterns. With the help of an assistant, he created more than 400 original works, many of which now hang in scientific workplaces including the headquarters of the American Society for Biochemisty and Biophysics, Amgen, the Caruthers Biotechnology Building at the University of Colorado in Boulder, Genentech, Google, the National Institutes of Health, and the Stanford University Center for Integrated Systems.

String Theory


Colored Triangles

Fusion


References

Photo CreditsCover photo by Stefan ArmijoCSHL Plasmid Biology Conference.

Photos courtesy of Cold Spring Harbor Laboratory.

DNA Foam Model. Photo courtesy of BioRad.

St. Francis Hotel, San Francisco, CA. Sergey Sus. CC BY-NC-ND 2.0.

Hambrecht & Quist Healthcare Conference Program, 1983. Courtesy of Annette Campbell White.

Robert Schimke. Courtesty of the Schimke family.

Philip Yeo. news.gov.sg.Biopolis Sign. A*STAR.Biopolis Building Complex. Henry

Leong Him Who. CC BY-SA 2.0.

St. John’s Chapel, Cambridge, UK. David Iliff. CC BY 3.0.

New MRC LMB, 2013. Bluesci.Sheikh Mohammed Bin Rashid

Al Maktoum. Twitter, @HHSkhMohd.

Dubiotech. Dubai Corporation of Tourism & Commerce Marketing.

Artist sketch of proposed Dubiotech HQ. DuBiotech media center.

Shenzhen, China. Sean Marshall. CC BY-NC 2.0.

Francis Collins at BGI. BGI.Illumina sequencers at BGI.

Scotted400, CC BY 3.0.Santiago, Chile, June 1, 2007. Victor

San Martin, CC BY-NC 2.0.

Pablo Valenzuela and Bernardita Mendez. Fundacion Ciencia & Vida.

Florence Wambugu. ICRAF/Sherry Odeyo.

Sorghum. United Sorghum Checkoff Program.

Bananas. Africa Harvest Biotech Foundation International.

Robert Briggs Watson. Rockefeller Archive Center.

Pan American Route Map, 1947. Airline Timetable images.

Robert Briggs Watson Diary. The Wilson Library, University of North Carolina.

Chinese hamster. Cherrelle Claywell.

Theodore Puck. American Journal of Human Genetics.

George Whitsides. Stephanie Mitchell.nsf.gov.

Three Device Set. Diagnostics for All.

Manzanar from Guard Tower. Ansel Adams. Library of Congress.

Gordon Sato, July 1944. UC Berkeley, Bancroft Library.

Gordon Sato on beach. The Manzanar Project.

Robert Schimke portrait and artwork. Courtesty of the Schimke family.

Global Biotech CentersBiomedical Research Council

(BMRC). The Biopolis Story: Commemorating Ten Years of Excellence. Singapore: A*STAR, 2013.

Poh, Lim Chuan. Speech at the Biopolis 10th Anniversary Gala Dinner. www.a-star.edu.sg. Accessed November 23, 2014.

Burn-Callander, Rebecca. “Cambridge University Spinoffs Get £50m Lifeline.” The Daily Telegraph. October 10, 2013.

Eltayeb, Salah Eldin. “Mohammed launches biotech park project.” Khaleej Times. February 2, 2005.

Köhler, Georges, and Cesar Milstein. "Continuous cultures of fused cells secreting antibody of predefined specificity." Nature 256, no. 5517 (1975): 495-497.

Rosen, Fred S. “The Specific Notion.” Nature 383 (1996): 777.

Sheridan, Cormac. “New Biotech Oasis?” Bioentrepreneur, June 30, 2005.

“UAE’s biotechnology industry challenges in focus.” TradeArabia, November 20, 2014. www.tradearabia.com/news/EDU_26998.html.

Biotech PhilanthropyAoyagi-Stom, Caroline. “A Love

of Science Breeds a Life of Humanity.” [dehai-news] Pacificcitizen.org. November 22, 2008.

“Smartphone-enabled vaccine checks.” Cambridge Consultants. December 9, 2013. cambridgeconsultants.com.

Vital Tools: A Brief History of CHO Cells.

Colaianni, C. Alessandra, and Robert M. Cook-Deegan. “Columbia University’s Axel Patents: Technology Transfer and Implications for the Bayh-Dole Act.” Milibank Quarterly 87, no. 3 (2009): 683-715.

Greenwood, David. Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. Oxford: Oxford University Press, 2008.

Hsieh, E. T. “A New Laboratory Animal (Cricetulus griseus).” National Medical Journal of China 5 (1919): 20-24.

Hou, Jeff Jia Cheng, Joe Codamo, Warren Pilbrough, Benjamin Hughes, Peter P. Gray and Trent P. Munro. “New Frontiers in Cell Line Development: Challenges for Biosimilars.” Journal of Chemical Technology and Biotechnology 86 (2011): 895-904.

Jayapal, Karthik P., Katie F. Wlaschin, Wei-Shou Hu, and Miranda G. S. Yap. “Recombinant Protein Therapeutics from CHO Cells—20 Years and Counting.” Chemical Engineering Progress 103, no. 10 (2007): 40-47.

Kleid, Dennis G., Ph.D. “Scientist and Patent Agent at Genentech.” An oral history conducted in 2001 and 2002 by Sally Smith Hughes for the Regional Oral History Office, the Bancroft Library, University of California, Berkeley, 2002.

Lopatto, Elizabeth. “Chinese Hamster Ovary Cells Could Make More Drugs, Alnylam Says.” Bloomberg, November 21, 2009.

Marcus, Philip I., Gordon H. Sato, Richard G. Ham, and David Patterson. "A tribute to Dr. Theodore T. Puck." In Vitro Cellular & Developmental Biology-Animal 42, no. 8 (2006): 235-241.

McAtee, Allison G., Neil Templeton, and Jamey D. Young. "Role of Chinese hamster ovary central carbon metabolism in controlling the quality of secreted biotherapeutic proteins." Pharmaceutical Bioprocessing 2, no. 1 (2014): 63-74.

“The New Drug War—Hard Pills to Swallow,” The Economist, January 4, 2014.

Puck, Theodore T. “Development of the CHO cell for use in Somatic Cell Genetics.” In Molecular Cell Genetics, edited by Michael Gottesman, 37-64. New York: John Wiley & Sons, 1985.

Scangos, George. Lecture, MIT Chemical Engineering Department, May 2, 2014.

Walsh, Gary. “Biopharmaceutical Benchmarks 2014.” Nature Biotechnology 32 (2014): 992-1000.

Watson, Robert Briggs. “Volume 4: 1947-1948,” in the Robert Briggs Watson Diary, #3844, Southern Historical Collection, The Wilson Library, University of North Carolina at Chapel Hill.

Wechsler, Alan. “Victor Schwentker: The gerbil genius and rat wrangler of Brant Lake,” Adirondack Life 34, No. 3 (2003): 22-27.

Wilson, Tazewell. “More Protein from Mammalian Cells.” Nature Biotechnology 2, no. 9 (1984): 753-755.

Wurm, Florian M. and David Hacker. “First CHO Genome.” Nature Biotechnology 29, no. 8 (2011): 718-20.

Wurm, Florian M. “CHO Quasispecies—Implications for Manufacturing Processes.” Processes 1, no. 3 (2013): 296-311.

Xu, Xun, et al. “The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.” Nature Biotechnology 29, no. 8 (2011): 735-741.

Yerganian, George. “History and Cytogenetics of Hamsters.” Progress in Experimental Tumor Research 16 (1972): 2-41

Yerganian, George. “Biology and Genetics of Chinese Hamsters.” In Molecular Cell Genetics, edited by Michael Gottesman. New York: John Wiley & Sons, 1985.

Brook Byers Kleiner Perkins Caufield & Byers

Heather Erickson Life Sciences Foundation

Carl Feldbaum, Chair Biotechnology Industry Organization

Frederick Frank EVOLUTION Life Science Partners

Dennis Gillings Quintiles Transnational

John Lechleiter Eli Lilly and Company

Scott Morrison EY

Ivor Royston Forward Ventures

Phillip Sharp MIT (Academic Advisor)

Henri Termeer Genzyme Corporation

Daniel Adams Protein Sciences

Sol Barer Celgene

James Blair Domain Associates

Joshua Boger Vertex Pharmaceuticals

William Bowes U.S. Venture Partners

Robert Carpenter Hydra Biosciences

Marc Casper Thermo Fisher Scientific

Nancy Chang Orbimed

Susan Desmond-Hellmann Gates Foundation

Jay Flatley Illumina

Chris Garabedian Sarepta Therapeutics

Alan Gold BioMed Realty

Joseph Goldstein UT Southwestern

James Greenwood Biotechnology Industry Organization

Harry Gruber Tocagen

David Hale Hale BioPharma Ventures

William Haseltine Access Health International

Paul Hastings OncoMed Pharmaceuticals

Sally Smith Hughes University of California, Berkeley

Perry Karsen Celgene

Rachel King Glycomimetics

Arthur Levinson Calico

Greg Lucier Life Technologies

Magda Marquet Ajinomoto Althea

David Meeker Genzyme Corporation

Alan Mendelson Latham & Watkins

Fred Middleton Sanderling Ventures

Tina Nova Illumina

Stelios Papadopoulos Exelixis

Richard Pops Alkermes

George Poste Arizona State University

Dennis Purcell Aisling Capital

Josef von Rickenbach PAREXEL

Roberto Rosenkranz Roxro Pharma

William Rutter Synergenics

George Scangos Biogen Idec

Steven Shapin Harvard University

Stephen Sherwin Ceregene

Jay Siegel Johnson & Johnson

Vincent Simmon Genex Corporation

Mark Skaletsky Fenway Pharmaceuticals

Thomas Turi Covance

J. Craig Venter J. Craig Venter Institute

Board of Advisors

Board of Directors

Affiliations for identification purposes

P.O. Box 2130 San Francisco, CA 94126

biotechhistory.org

LSF Magazine Winter 2015

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